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Comprehensive analysis of the role of SFXN family in breast cancer

  • Ding Yuan EMAIL logo , Jialiang Liu , Wenbo Sang and Qing Li
Published/Copyright: April 1, 2023
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Open Medicine
From the journal Open Medicine Volume 18 Issue 1

Abstract

The sideroflexin (SFXN) family is a group of mitochondrial membrane proteins. Although the function of the SFXN family in mitochondria has been widely recognized, the expression levels, role, and prognostic value of this family in breast cancer (BC) have not been clearly articulated and systematically analysed. In our research, SFXN1 and SFXN2 were significantly upregulated in BC versus normal samples based on Gene Expression Profiling Interactive Analysis 2 and the Human Protein Atlas databases. We found that high SFXN1 expression was significantly related to poor prognosis in BC patients and that high SFXN2 expression was significantly associated with good prognosis in BC patients. Gene Ontology analysis of the SFXN family was performed based on the STRING database to explore the potential functions of this family, including biological processes, cellular components, and molecular functions. Based on the MethSurv database, we found that two SFXN1 CpG sites (5′-UTR-S_Shelf-cg06573254 and TSS200-Island-cg17647431), two SFXN2 CpG sites (3′-UTR-Open_Sea-cg04774043 and Body-Open_Sea-cg18994254), one SFXN3 CpG site (Body-S_Shelf-cg17858697), and nine SFXN5 CpG sites (1stExon;5′-UTR-Island-cg03856450, Body-Open_Sea-cg04016113, Body-Open_Sea-cg04197631, Body-Open_Sea-cg07558704, Body-Open_Sea-cg08383863, Body-Open_Sea-cg10040131, Body-Open_Sea-cg10588340, Body-Open_Sea-cg17046766, and Body-Open_Sea-cg22830638) were significantly related to the prognosis of BC patients. According to the ENCORI database, four negative regulatory miRNAs for SFXN1 (hsa-miR-22-3p, hsa-miR-140-5p, hsa-miR-532-5p, and hsa-miR-582-3p) and four negative regulatory miRNAs for SFXN2 (hsa-miR-9-5p, hsa-miR-34a-5p, hsa-miR-532-5p, and hsa-miR-885-5p) were related to poor prognosis for BC patients. This study suggests that SFXN1 and SFXN2 are valuable biomarkers and treatment targets for patients with BC.

Keywords: sideroflexin; breast cancer; biomarkers; prognosis

1 Introduction

Breast cancer (BC) is a common type of cancer in women and a major cause of cancer death, and the incidence of BC is increasing worldwide [1,2]. BC is caused by multiple factors (genetic, hormonal, and environmental); in particular, gene mutation plays an important role in the occurrence and development of BC [3,4]. At present, with the rise of personalized treatment for BC, both the oestrogen receptor and human epidermal growth factor receptor 2 have been confirmed as therapeutic targets for BC, and many BC patients benefit from them [5,6,7,8]. However, more markers need to be discovered for clinical application in the precise therapy of BC patients.

The members of the sideroflexin (SFXN) family are mitochondrial membrane proteins. The SFXN family has five members, namely, SFXN1, SFXN2, SFXN3, SFXN4, and SFXN5, which are classified in SLC56 [9]. SFXN1 acts as a mitochondrial serine transporter in single-carbon metabolism [10]. SFXN1 deficiency causes damage to the mitochondrial respiratory chain, compromising the biosynthesis, activity, and assembly of complex III (CIII) and reducing the level of coenzyme Q [11]. Mon et al. reported that SFXN2 is a mitochondrial outer membrane protein that plays a role in mitochondrial iron homeostasis by regulating haem biosynthesis [12]. Chen et al. reported that upregulated SFXN2 expression limits mitochondrial autophagy and increases iron-mediated energy production to promote the proliferation of multiple myeloma cells [13]. SFXN3 is an α-synuclein-dependent mitochondrial protein that regulates synaptic morphology and affects neurodegenerative pathways in humans [14,15]. SFXN4 is a complex I assembly factor, and SFXN4 deficiency causes macrocytic anaemia and mitochondrial disease [16,17]. Yoshikumi et al. reported that the expression level of SFXN5 in the pancreatic islets of rats with streptozotocin-induced diabetes was upregulated compared with that in normal rats [18]. However, although the role of the SFXN family in some cancers, such as lung adenocarcinoma and myeloma, has been studied in recent years [13,19], the expression and potential carcinogenic effects of the SFXN family in BC have not been clearly reported.

To elucidate the potential role of the SFXN family in BC, we performed systematic bioinformatics analysis of the SFXN family in BC, including expression patterns, functions, and prognostic value for BC patients. In addition, miRNAs that might regulate the expression of SFXN1 and SFXN2 in BC were found, and miRNA‒mRNA interaction had an impact on the prognosis of BC patients. This study advances the state of knowledge regarding the SFXN family in BC.

2 Materials and methods

2.1 Gene expression profiling interactive analysis 2 (GEPIA) analysis

GEPIA2 [20] (http://gepia2.cancer-pku.cn/) is a Web server that analyses RNA sequencing expression data from 9,736 tumours and 8,587 normal samples of TCGA and GTEx datasets using standard processing pipelines. We used GEPIA2 database to analyse the RNA expression level of SFXN family and ten nearest neighbour genes significantly related to SFXN1 and SFXN2 in BC samples. In addition, we explored the correlation among SFXN1–SFXN5 based on GEPIA2 database.

2.2 Human protein atlas (HPA) analysis

All data in the HPA [21] (https://www.proteinatlas.org/about) database is open access, allowing scientists in academia and industry to freely access the data to explore the human proteome. We detected the expression levels of SFXN1–SFXN5 in BC tissues compared with normal tissues. The antibodies used in the database were HPA063745, HPA018150, HPA008028, HPA020872, and HPA015473.

2.3 Survival analysis

Using Kaplan–Meier plotter [22] (http://www.kmplot.com/), we analysed the impact of SFXN family on the survival rate of patients with BC. Moreover, 1086 BC patients’ data from the TCGA database were collected to verify the results from Kaplan–Meier plotter database.

2.4 cBioPortal analysis

Based on cBioPortal [23] (https://www.cbioportal.org) database, we chose the Invasive Breast Carcinoma database (METABRIC, Nature 2012, and Nat Commun 2016) to explore and construct the BC genome atlas of the SFXN family.

2.5 STRING analysis

STRING [24] (https://string-db.org) database was used to establish an SFXN family protein network to explore the potential function of the SFXN family.

2.6 DNA methylation analysis

MethSurv [25] (https://biit.cs.ut.ee/methsurv/) database is a web tool that can perform multivariable survival analysis using DNA methylation data. We used MethSurv database to explore the relationship between SFXN family methylation sites and prognostic value in BC patients.

2.7 TISIDB analysis

TISIDB [26] (http://cis.hku.hk/TISIDB/) database is a web portal for tumour and immune system interaction, which integrates multiple heterogeneous data types. Using TISIDB database, we analysed the relations between abundance of tumour-infiltrating lymphocytes and SFXN1 and SFXN2 expression. In addition, distributions of SFXN1 and SFXN2 expression across immune and molecular subtypes were also shown in our research.

2.8 ENCORI analysis

Using ENCORI [27] (http://starbase.sysu.edu.cn/panCancer.php) database, we predicted some miRNAs that regulated SFXN1 and SFXN2 expression in BC. Analysis parameters were medium stringency (≥3) and one cancer type.

2.9 Statistical analysis

Using Student’s t-tests, the statistical difference between the SFXN family mRNA expression level in BC and normal samples was revealed. Based on log-rank test and hazard ratio (HR), Kaplan–Meier plotter was used to draft survival curves that could reveal the relation between the expression of SFXN family and prognostic value of BC patients. P < 0.05 was considered to be statistically significant. Statistical analysis and visualization were done using R-project (version 3.6.3).

3 Results

3.1 Transcriptional levels of SFXN family in BC patients

Using GEPIA2 database, the transcriptional levels of the SFXN family were analysed to reveal the statistical difference between the SFXN family mRNA expression level in BC and normal samples. We found that SFXN1 and SFXN2 mRNA transcriptional levels were significantly upregulated in BC samples compared with normal samples, but not SFXN3–SFXN5 (Figure 1a). Furthermore, based on the immunohistochemistry results from HPA database, SFXN1 (antibody: HPA063745) and SFXN2 (antibody: HPA018150) were overexpressed in BC tissues versus normal breast tissues (Figure 1b and c). The expression levels of SFXN3 (antibody: HPA008208), SFXN4 (antibody: HPA020872), and SFXN5 (antibody: HPA015473) in BC tissues were not significantly upregulated compared to normal breast tissues (Figure 1d–f).

Figure 1 The transcriptional levels of SFXN1–SFXN5 in BC. (a) The transcriptional levels of SFXN1–SFXN5 were analysed based on GEPIA2 database. *P < 0.05. (b) SFXN1 (antibody: HPA063745) and (c) SFXN2 (antibody: HPA018150) were overexpressed in BC tissues versus normal breast tissues by immunohistochemistry based on HPA database, but not (d) SFXN3 (antibody: HPA008208), (e) SFXN4 (antibody: HPA020872), and (f) SFXN5 (antibody: HPA015473). (g) Prognostic value of the expression levels of SFXN1–SFXN5 in BC patients based on Kaplan–Meier plotter.
Figure 1

The transcriptional levels of SFXN1–SFXN5 in BC. (a) The transcriptional levels of SFXN1–SFXN5 were analysed based on GEPIA2 database. *P < 0.05. (b) SFXN1 (antibody: HPA063745) and (c) SFXN2 (antibody: HPA018150) were overexpressed in BC tissues versus normal breast tissues by immunohistochemistry based on HPA database, but not (d) SFXN3 (antibody: HPA008208), (e) SFXN4 (antibody: HPA020872), and (f) SFXN5 (antibody: HPA015473). (g) Prognostic value of the expression levels of SFXN1–SFXN5 in BC patients based on Kaplan–Meier plotter.

3.2 Prognostic value of SFXN family in clinical patients with BC

Using Kaplan–Meier plotter, we explored the impact of the SFXN family expression on the overall survival (OS) rate of BC patients. As shown in Figure 1g, upregulated mRNA expression levels of SFXN1 were significantly related to poor prognosis in BC patients (HR = 1.39, P = 0.00054) but increased SFXN2 expression was significantly associated with good prognosis in patients with BC (HR = 0.55, P = 1.3 × 10−5). We did not find the relationships between SFXN3-5 expression and prognosis in BC patients. A TCGA cohort of 1086 BC patients also verified the above-mentioned results (Figure S1).

3.3 Alterations, correlations, and potential role analysis among SFXN family members

We detected the alterations of SFXN1–SFXN5 in BC by the cBioPortal database. We found that SFXN1–SFXN5 were altered in 348 of the 2509 BC samples (14%), including amplification, deep deletion, high mRNA expression, and low mRNA expression (Figure 2a). Using the GEPIA2 database, the correlations of SFXN family members in BC were analysed. As shown in Figure 2b, the results were as follows: SFXN1–SFXN2 (R = 0.24), SFXN1–SFXN3 (R = 0.26), SFXN1–SFXN4 (R = −0.0033), SFXN1–SFXN5 (R = 0.14), SFXN2–SFXN3 (R = 0.19), SFXN2–SFXN4 (R = 0.079), SFXN2–SFXN5 (R = 0.17), SFXN3–SFXN4 (R = −0.11), SFXN3–SFXN5 (R = 0.31), and SFXN4–SFXN5 (R = 0.02).

Figure 2 Alterations and correlation between members of SFXN family in BC. (a) SFXN family expression and alterations in BC based on cBioPortal. (b) Correlation analysis between SFXN family members in BC based on GEPIA.
Figure 2

Alterations and correlation between members of SFXN family in BC. (a) SFXN family expression and alterations in BC based on cBioPortal. (b) Correlation analysis between SFXN family members in BC based on GEPIA.

Furthermore, in order to explore the potential function of the SFXN family, Gene Ontology (GO) analysis for the SFXN family was performed to predict the potential functions of the SFXN family based on STRING database, including biological processes (BPs), cellular components, and molecular functions. We found that GO:1990542 (mitochondrial transmembrane transport), GO:0006730 (one-carbon metabolic process), GO:0006865 (amino acid transport), GO:0022889 (serine transmembrane transporter activity), GO:0046943 (carboxylic acid transmembrane transporter activity), GO:0015075 (ion transmembrane transporter activity), and GO:0031305 (integral component of mitochondrial inner membrane) were significantly regulated by alterations in the SFXN family (Table 1). The important roles of the SFXN family in mitochondrial transmembrane transport and one-carbon metabolic process have been widely recognized.

Table 1

Functional annotation enrichment analysis of SFXN family performed by STRING database

GO term Count False discovery rate (FDR)
GO:1990542 (mitochondrial transmembrane transport) 5 4.05 × 10−8
BP GO:0006730 (one-carbon metabolic process) 2 0.0288
GO:0006865 (amino acid transport) 5 9.67 × 10−8
GO:0022889 (serine transmembrane transporter activity) 3 5.60 × 10−6
MF GO:0046943 (carboxylic acid transmembrane transporter activity) 4 3.29 × 10−5
GO:0015075 (ion transmembrane transporter activity) 5 9.26 × 10−5
CC GO:0031305 (integral component of mitochondrial inner membrane) 5 2.04 × 10−10

3.4 Relationship between SFXN family methylation sites and prognostic value in BC patients

MethSurv database was used to perform multivariable survival analysis to reveal the relationship between SFXN1 and SFXN2 methylation sites and prognosis in BC patients. The methylation profiles of SFXN1 and SFXN2 were obtained from MethSurv database. We found that 13 SFXN1 CpG sites (Figure 3a), of which 2 CpG sites (5′-UTR-S_Shelf-cg06573254 and TSS200-Island-cg17647431) were significantly related to the prognosis of BC patients (Table 2). Four SFXN2 CpG sites (Figure 3b) were found, of which two CpG sites (3′-UTR-Open_Sea-cg04774043 and Body-Open_Sea-cg18994254) were significantly associated with the prognosis of BC patients (Table 3). Five SFXN3 CpG sites (Figure 3c) were found, of which one CpG site (Body-S_Shelf-cg17858697) was significantly related to the prognosis of BC patients (Table 4). Moreover, we found that 29 SFXN5 CpG sites (Figure 3e), of which 9 CpG sites (5′-UTR-S_Shelf-cg06573254 and TSS200-Island-cg17647431) were significantly associated with the prognosis of BC patients (Table 5). However, we did not find correlations between SFXN4 CpG sites and prognosis in BC patients (Figure 3d and Table 6).

Figure 3 The relationship between SFXN1 and SFXN2 methylation sites and prognostic value in BC patients. (a) Heat map for SFXN1 in BC. (b) Heat map for SFXN2 in BC. (c) Heat map for SFXN3 in BC. (d) Heat map for SFXN4 in BC. (e) Heat map for SFXN5 in BC.
Figure 3

The relationship between SFXN1 and SFXN2 methylation sites and prognostic value in BC patients. (a) Heat map for SFXN1 in BC. (b) Heat map for SFXN2 in BC. (c) Heat map for SFXN3 in BC. (d) Heat map for SFXN4 in BC. (e) Heat map for SFXN5 in BC.

Table 2

Effect of hypermethylation level of SFXN1 on prognosis in BC

CpG HR CI P Value
TSS200-Island-cg00075204 0.804 (0.505–1.28) 0.357016246
TSS200-Island-cg02277511 1.218 (0.763–1.945) 0.408550216
5′-UTR-S_Shelf-cg06573254 0.587 (0.359–0.958) 0.033011463
TSS1500-N_Shore-cg07293947 0.758 (0.472–1.216) 0.249926515
TSS200-Island-cg07590632 0.8 (0.486–1.318) 0.381746405
5′-UTR-Island-cg09801842 1.176 (0.749–1.847) 0.481301929
5′-UTR-S_Shore-cg13581034 0.663 (0.437–1.006) 0.053534213
5′-UTR-Open_Sea-cg13725579 0.723 (0.491–1.066) 0.10171772
TSS200-Island-cg14735227 0.7 (0.436–1.123) 0.139380396
TSS200-Island-cg17647431 0.477 (0.318–0.715) 0.000337326
Body-Open_Sea-cg17747551 1.529 (0.945–2.683) 0.080503652
(1stExon;5′-UTR)-Island-cg25632300 0.701 (0.455–1.082) 0.108483031
5′-UTR-Open_Sea-cg27626110 1.157 (0.756–1.772) 0.501969845

Bold values are used for information with P < 0.05.

Table 3

Effect of hypermethylation level of SFXN2 on prognosis in BC

CpG HR CI P Value
3′-UTR-Open_Sea-cg04774043 0.597 (0.403–0.885) 0.010100815
Body-Open_Sea-cg14863667 0.674 (0.446–1.021) 0.062516563
Body-Open_Sea-cg18994254 0.495 (0.332–0.736) 0.000527837
5′-UTR-S_Shelf-cg24960641 0.838 (0.53–1.324) 0.448366312

Bold values are used for information with P < 0.05.

Table 4

Effect of hypermethylation level of SFXN3 on prognosis in BC

CpG HR CI P Value
3′-UTR-N_Shore-cg13460073 1.137 (0.773–1.674) 0.513879699
Body-S_Shore-cg15428620 0.664 (0.403–1.093) 0.107383131
Body-S_Shelf-cg17858697 0.407 (0.227–0.73) 0.002523129
Body-S_Shore-cg18132852 0.635 (0.385–1.046) 0.0745156
Body-S_Shelf-cg19842683 1.469 (0.817–2.64) 0.19858941

Bold values are used for information with P < 0.05.

Table 5

Effect of hypermethylation level of SFXN5 on prognosis in BC

CpG HR CI P Value
Body-Island-cg02340378 0.763 (0.476–1.224) 0.261905244
TSS200-Island-cg03077062 1.106 (0.75–1.632) 0.610669504
(1stExon;5′-UTR)-Island-cg03856450 0.63 (0.419–0.948) 0.026834993
Body-Open_Sea-cg04016113 0.385 (0.219–0.677) 0.000916438
Body-Open_Sea-cg04197631 0.638 (0.432–0.943) 0.024000916
Body-Open_Sea-cg05062556 1.565 (0.916–2.673) 0.101212683
TSS200-Island-cg05539622 0.737 (0.477–1.139) 0.169875526
Body-Open_Sea-cg05997270 1.492 (0.874–2.548) 0.142590859
TSS1500-S_Shore-cg06191390 1.075 (0.667–1.731) 0.767367535
3′-UTR-Open_Sea-cg06898946 1.565 (0.917–2.669) 0.100221362
TSS1500-S_Shore-cg07452306 1.247 (0.811–1.917) 0.314599158
Body-Open_Sea-cg07558704 0.549 (0.326–0.925) 0.024167969
TSS200-Island-cg07842862 0.629 (0.373–1.059) 0.080831914
Body-Open_Sea-cg08060322 0.731 (0.443–1.203) 0.217589883
Body-Open_Sea-cg08383863 0.497 (0.291–0.849) 0.010445105
Body-Open_Sea-cg08461546 1.117 (0.757–1.646) 0.577394194
1stExon-Island-cg08973851 1.265 (0.806–1.987) 0.306727837
Body-Open_Sea-cg10040131 1.85 (1.083–3.159) 0.02423507
Body-Open_Sea-cg10588340 0.566 (0.336–0.954) 0.032586494
Body-Island-cg14497869 1.383 (0.908–2.108) 0.131331579
Body-Open_Sea-cg17046766 1.604 (1.035–2.485) 0.034460369
Body-N_Shore-cg17639959 0.78 (0.509–1.193) 0.251790437
TSS200-Island-cg18358762 0.772 (0.522–1.141) 0.19455617
Body-Open_Sea-cg20584546 1.199 (0.811–1.771) 0.362740545
Body-Open_Sea-cg22830638 1.497 (1.006–2.228) 0.046907355
TSS200-Island-cg23396786 0.853 (0.535–1.358) 0.502214225
Body-Open_Sea-cg24803346 1.328 (0.891–1.979) 0.163122628
TSS200-Island-cg26664455 0.877 (0.594–1.293) 0.506775452
Body-Open_Sea-cg27557525 1.347 (0.887–2.046) 0.161840548

Bold values are used for information with P < 0.05.

Table 6

Effect of hypermethylation level of SFXN4 on prognosis in BC

CpG HR CI P Value
TSS200-Island-cg00039793 1.537 (0.961–2.459) 0.072648992
TSS200-Island-cg02699461 0.595 (0.349–1.015) 0.056815652
Body-N_Shore-cg03745912 1.301 (0.826–2.05) 0.256731252
(1stExon;5′-UTR)-Island-cg04466870 0.85 (0.571–1.267) 0.424668793
TSS1500-Island-cg09733103 0.669 (0.423–1.057) 0.084919658
3′-UTR-Open_Sea-cg15803556 0.765 (0.518–1.13) 0.17824569
(1stExon;5′-UTR)-Island-cg19587168 1.124 (0.762–1.657) 0.556229052
1stExon-Island-cg20254282 1.259 (0.793–1.998) 0.329115199
TSS200-Island-cg23788592 0.879 (0.556–1.388) 0.579432626
Body-N_Shelf-cg25713214 0.692 (0.428–1.118) 0.132244808
Body-Island-cg26649219 1.106 (0.751–1.628) 0.611426216

3.5 SFXN1 and SFXN2 expression levels are associated with immune and molecular subtypes and immune cell infiltration in BC

Next, we explored the roles of the SFXN1 and SFXN2 expression on immune and molecular subtypes in BC based on TISIDB database. The immune subtypes were classified into six types, namely, C1 (wound healing), C2 (IFN-gamma dominant), C3 (inflammatory), C4 (lymphocyte depleted), C5 (immunologically quiet), and C6 (TGF-b dominant). Our results showed that the SFXN1 and SFXN2 expression levels were significantly related to immune subtypes in BC (Figure S2a and b). Moreover, we also found that the SFXN1 and SFXN2 expression levels were significantly associated with molecular subtypes in BC (Figure S2c and d).

In addition, the relationships between abundance of tumour-infiltrating lymphocytes and SFXN1 and SFXN2 expression levels are given in Tables 7 and 8. We found that SFXN1 expression was significantly related to activated B cell (R = −0.323, P = 2.2 × 10−16), and SFXN2 expression was significantly associated with effector memory CD8T cell (R = 0.328, P = 2.2 × 10−16), T follicular helper cell (R = −0.393, P = 2.2 × 10−16), gamma delta T cell (R = −0.335, P = 2.2 × 10−16), type 1 T helper cell (R = −0.378, P = 2.2 × 10−16), regulatory T cell (R = −0.31, P = 2.2 × 10−16), myeloid-derived suppressor cell (R = −0.307, P = 2.2 × 10−16), natural killer T cell (R = −0.354, P = 2.2 × 10−16), and activated dendritic cell (R = −0.325, P = 2.2 × 10−16). These results indicated that SFXN1 and SFXN2 expression levels played essential roles in the immune cell infiltration in BC.

Table 7

Relations between abundance of tumour-infiltrating lymphocytes and SFXN1 expression in breast cancer

Description Correlation P value
Activated CD8T cell −0.149 7.08 × 10−7
Central memory CD8T cell 0.065 0.0308
Effector memory CD8T cell −0.256 8.11 × 10−18
Activated CD4T cell 0.057 0.0579
Central memory CD8T cell −0.244 2.46 × 10−16
Effector memory CD8T cell 0.022 0.459
T follicular helper cell −0.223 8.33 × 10−14
Gamma delta T cell −0.196 5.45 × 10−11
Type 1 T helper cell −0.285 5.63 × 10−22
Type 17 T helper cell −0.235 3.93 × 10−15
Type 2 T helper cell −0.02 0.498
Regulatory T cell −0.113 0.000183
Activated B cell −0.323 2.2 × 10−16
Immature B cell −0.149 7.67 × 10−7
Memory B cell −0.051 0.0923
Natural killer cell −0.171 1.18 × 10−8
CD56natural killer cell −0.269 1.5 × 10−19
CD56dim killer cell −0.198 4.08 × 10−11
Myeloid-derived suppressor cell −0.192 1.48 × 10−10
Natural killer T cell −0.282 1.75 × 10−21
Activated dendritic cell −0.06 0.0466
Plasmacytoid dendritic cell −0.212 1.38 × 10−12
Immature dendritic cell −0.011 0.717
Macrophage −0.208 3.93 × 10−12
Eosinophil −0.173 8.95 × 10−9
Mast cell −0.292 4.31 × 10−31
Monocyte −0.167 2.52 × 10−8
Neutrophil −0.11 0.000249

Bold values are used for information with P < 0.05.

Table 8

Relations between abundance of tumour-infiltrating lymphocytes and SFXN2 expression in breast cancer

Description Correlation P value
Activated CD8T cell −0.212 1.42 × 10−12
Central memory CD8T cell −0.018 0.541
Effector memory CD8T cell 0.328 2.2 × 10−16
Activated CD4T cell −0.254 1.48 × 10−17
Central memory CD4T cell −0.263 9.54 × 10−19
Effector memory CD4T cell −0.142 2.31 × 10−6
T follicular helper cell −0.393 2.2 × 10−16
Gamma delta T cell −0.335 2.2 × 10−16
Type 1 T helper cell −0.378 2.2 × 10−16
Type 17 T helper cell −0.234 5.18 × 10−15
Type 2 T helper cell −0.246 1.49 × 10−16
Regulatory T cell −0.31 2.2 × 10−16
Activated B cell −0.252 2.61 × 10−17
Immature B cell −0.189 3.06 × 10−10
Memory B cell −0.177 3.67 × 10−9
Natural killer cell −0.133 1 × 10−5
CD56 natural killer cell −0.219 2.63 × 10−13
CD56dim killer cell −0.264 6.29 × 10−19
Myeloid-derived suppressor cell −0.307 2.2 × 10−16
Natural killer T cell −0.354 2.2 × 10−16
Activated dendritic cell −0.325 2.2 × 10−16
Plasmacytoid dendritic cell −0.153 3.73 × 10−7
Immature dendritic cell 0.023 0.439
Macrophage −0.218 2.82 × 10−13
Eosinophil −0.075 0.0123
Mast cell −0.204 1.02 × 10−11
Monocyte −0.219 2.13 × 10−13
Neutrophil −0.045 0.135

Bold values are used for information with P < 0.05.

3.6 Immune cell-type expression and expression cluster analysis for SFXN1 and SFXN2

Furthermore, we explored the expression of immune cell types and expression clusters for SFXN1 and SFXN2. We found that SFXN1 was predominantly expressed in basophils (Figure 4a) and was a part of cluster basophil–DNA binding. Ten nearest neighbour genes significantly related to SFXN1 in basophil–DNA binding clusters were identified based on immune cell RNA expression, namely, FBLN5, KLHL35, ENPP2, RAB3GAP2, CCDC126, HRH4, HPGD, CD244, C10orf82, and CACNA1D (Table 9). Moreover, we also found that SFXN2 was low immune cell specificity (Figure 4b) and was a part of the T cell–unknown function cluster. Ten nearest neighbour genes significantly associated with SFXN2 in T cell–unknown function cluster were identified based on immune cell RNA expression, namely, ZNF563, SLC9A3, CFAP70, C14orf132, METAP1D, FAM153A, TRABD2A, ST3GAL3, REV1, and WNK3 (Table 10). As shown in Figure S3a, FBLN5, KLHL35, ENPP2, and HPGD were significantly overexpressed in BC compared with normal samples. However, we did not find any gene significantly associated with SFXN2 in the T cell–unknown function cluster, which was significantly upregulated in BC versus normal samples (Figure S3b). Furthermore, our results indicated that high expression of ENPP2, FBLN5, HPGD, and KLHL35 was significantly related to good prognosis for BC patients (Figure S4).

Figure 4 Expression of immune cell types and expression cluster analysis for SFXN1 and SFXN2. (a) SFXN1 was predominantly expressed in basophils. (b) SFXN2 was low immune cell specificity.
Figure 4

Expression of immune cell types and expression cluster analysis for SFXN1 and SFXN2. (a) SFXN1 was predominantly expressed in basophils. (b) SFXN2 was low immune cell specificity.

Table 9

Ten nearest neighbour genes significantly related to SFXN1 in Basophil–DNA binding cluster based on immune cell RNA expression

Neighbour Description Correlation
FBLN5 Fibulin 5 0.7909
KLHL35 Kelch-like family member 35 0.7869
ENPP2 Ectonucleotide pyrophosphatase/phosphodiesterase 2 0.7815
RAB3GAP2 RAB3 GTPase-activating noncatalytic protein subunit 2 0.7780
CCDC126 Coiled-coil domain containing 126 0.7691
HRH4 Histamine receptor H4 0.7664
HPGD 15-hydroxyprostaglandin dehydrogenase 0.7628
CD244 CD244 molecule 0.7562
C10orf82 Chromosome 10 open reading frame 82 0.7544
CACNA1D Calcium voltage-gated channel subunit alpha1 D 0.7504
Table 10

Ten nearest neighbour genes significantly related to SFXN2 in T cells–unknown function cluster based on immune cell RNA expression

Neighbour Description Correlation
ZNF563 Zinc finger protein 563 0.7651
SLC9A3 Solute carrier family 9 member A3 0.7642
CFAP70 Cilia and flagella-associated protein 70 0.7482
C14orf132 Chromosome 14 open reading frame 132 0.7433
METAP1D Methionyl aminopeptidase type 1D, mitochondrial 0.7143
FAM153A Family with sequence similarity 153 member A 0.7077
TRABD2A TraB domain containing 2A 0.7010
ST3GAL3 ST3 beta-galactoside alpha-2,3-sialyltransferase 3 0.6877
REV1 REV1 DNA-directed polymerase 0.6872
WNK3 WNK lysine-deficient protein kinase 3 0.6694

3.7 Regulatory miRNA analysis for SFXN1 and SFXN2 in BC

As shown in Tables S1 and S2, 173 miRNAs regulating SFXN1 and 97 miRNAs regulating SFXN2 were predicted based on ENCORI database. Among them, 132 miRNA–SFXN1 pairs and 79 miRNA–SFXN2 pairs were negatively correlated. As shown in Figure 5a, four negative regulatory miRNA–SFXN1 pairs were significantly related to poor prognosis for BC patients, namely, has-miR-22-3p (HR = 1.88, P = 0.00015) [28], has-miR-140-5p (HR = 1.40, P = 0.041), has-miR-532-5p (HR = 1.39, P = 0.044), and has-miR-582-3p (HR = 1.38, P = 0.049). Moreover, as shown in Figure 5b, four negative regulatory miRNA–SFXN2 pairs were significantly associated with poor prognosis for BC patients and miRNAs negatively regulated SFXN2, namely, has-miR-9-5p (HR = 1.67, P = 0.0019), has-miR-34a-5p (HR = 1.53, P = 0.0092), has-miR-532-5p (HR = 1.39, P = 0.044), and has-miR-885-5p (HR = 1.48, P = 0.029). The above-mentioned results suggest that the established miRNA–SFXN1 and miRNA–SFXN2 regulatory networks may be valuable prognostic markers and therapeutic targets for BC (Figure 5c).

Figure 5 The miRNA expression in BC predicted to regulate SFXN1 and SFXN2 and related to the prognosis of BC patients. (a) has-miR-22-3p, has-miR-140-5p, has-miR-532-5p, and has-miR-582-3p were related to poor OS in BC patients. (b) has-miR-9-5p, has-miR-34a-5p, has-miR-532-5p, and has-miR-885-5p were associated with poor OS in BC patients. (c) miRNA–SFXN1 and miRNA–SFXN2 regulation networks.
Figure 5

The miRNA expression in BC predicted to regulate SFXN1 and SFXN2 and related to the prognosis of BC patients. (a) has-miR-22-3p, has-miR-140-5p, has-miR-532-5p, and has-miR-582-3p were related to poor OS in BC patients. (b) has-miR-9-5p, has-miR-34a-5p, has-miR-532-5p, and has-miR-885-5p were associated with poor OS in BC patients. (c) miRNA–SFXN1 and miRNA–SFXN2 regulation networks.

4 Discussion

At present, the role of the SFXN family in BC has not been clearly reported. Using bioinformatics tools, this study systematically explored different aspects of the SFXN family in BC, including expression, prognosis, methylation, immune infiltration, and regulatory miRNA analysis. We found that SFXN1 and SFXN2 mRNA transcriptional levels were significantly upregulated in BC, but the same was not true of SFXN3–SFXN5. High SFXN1 expression was significantly related to poor prognosis in BC patients, but increased SFXN2 expression was significantly associated with good prognosis in patients with BC. Moreover, some CpG sites of the SFXN family were associated with the prognosis of BC patients. It has been reported that SFXN1 is overexpressed in head and neck squamous cell carcinoma and that high SFXN1 expression in this context is significantly associated with poor prognosis [29]. Jiang et al. reported that upregulated SFXN1 expression is significantly related to poor prognosis in lung adenocarcinoma patients [30]. In addition, it has been reported that SFXN2 is present in four different cancer types, namely, kidney cancer, urothelial cancer, cervical cancer, and liver cancer; only for kidney cancer is SFXN2 favourable [31].

Next, we performed GO analysis of the SFXN family to predict its potential functions. We found that the GO terms such as mitochondrial transmembrane transport, one-carbon metabolic process, amino acid transport, serine transmembrane transporter activity, carboxylic acid transmembrane transporter activity, ion transmembrane transporter activity, and integral component of mitochondrial inner membrane were significantly regulated by alterations in the SFXN family. The roles of SFXN1 and SFXN2 in mitochondria have been widely recognized. SFXN1 plays an important role in mitochondrial single-carbon metabolism, and SFXN1-mediated serine transport from the cytoplasm to mitochondria can be promoted by SERAC1 [10,32]. Moreover, SFXN1 deficiency causes damage to the mitochondrial respiratory chain, compromising CIII biosynthesis [11]. SFXN2 is a mitochondrial outer membrane protein that plays a role in mitochondrial iron homeostasis by regulating haem biosynthesis [12]. In addition, Pott et al. reported that SFXN2 expression was able to affect plaque burden in carotid arteries [33].

Furthermore, we explored the expression in immune cell types and expression clusters for SFXN1 and SFXN2. We found that SFXN1 was predominantly expressed in basophils and was a part of the basophil–DNA binding cluster. Four nearest neighbor genes significantly associated with SFXN1 in the basophil–DNA binding cluster were identified, namely, FBLN5, KLHL35, ENPP2, and HPGD, which were significantly overexpressed in BC compared with normal samples and related to good prognosis in BC patients. It has been reported that FBLN5 inhibits the proliferation and invasion of BC cells by downregulating Ki-67 [34]. Mao et al. reported that hsa-miR-370-3p promoted BC progression by inhibiting FBLN5 expression and activating the NF-κB signalling pathway [35]. KLHL35 is highly expressed in colon cancer tissues compared with normal samples and is associated with poor prognosis in colon cancer patients [36]. ENPP2 autocrine motility factor expression levels can be promoted by integrin alpha6beta4 in BC cells [37]. Lehtinen et al. reported that HPGD was highly expressed in metastatic and invasive BCs [38]. However, we did not find any gene significantly associated with SFXN2 in the T cell–unknown function cluster, which was significantly upregulated in BC versus normal samples.

MicroRNA expression is related to tumour occurrence, progression, and therapy, indicating that microRNAs may be useful as prognostic and predictive markers [39]. We identified eight negatively correlated miRNA–SFXN1 and miRNA–SFXN2 pairs, namely hsa-miR-22-3p–SFXN1, hsa-miR-140-5p–SFXN1, hsa-miR-582-3p–SFXN1, hsa-miR-532-5p–SFXN1, hsa-miR-9-5p–SFXN2, hsa-miR-34a-5p–SFXN2, hsa-miR-532-5p–SFXN2, and hsa-miR-885-5p–SFXN2, which might regulate SFXN1 and SFXN2 expression in BC and were used to explore the prognosis of BC patients. Functionally, decreased expression of hsa-miR-22-3p was related to good prognosis for BC patients [28]. It has been reported that hsa-miR-140-5p inhibits the proliferation of BC stem cells by targeting Wnt1 [40]. Huang et al. reported that hsa-miR-532-5p promoted BC proliferation and migration by targeting ras-related and oestrogen-regulated growth inhibitor [41]. The expression level of hsa-miR-9-5p is significantly increased in the serum of BC patients versus healthy controls and predicts poor prognosis for BC patients [42]. Maroni et al. reported that hsa-miR-34a-5p was upregulated in nonmetastatic breast carcinoma [43]. It has been reported that hsa-miR-885-5p can be a potential predictor of anthracycline-induced troponin elevation in BC patients [44]. However, the role of hsa-miR-582-3p in BC has not been reported. Our research could enrich the prognostic value of miRNAs regulating SFXN1 and SFXN2 in BC, which would be helpful for the discovery of BC markers and precise treatment targets.

5 Conclusion

In this study, we systematically analysed the expression levels, functions, and prognostic values of SFXN family in BC. Our results suggest that elevated SFXN1 and SFXN2 play essential roles in BC. High SFXN1 expression was significantly related to poor prognosis in BC patients, and high SFXN2 expression was significantly associated with good prognosis in patients with BC. Moreover, we found that two SFXN1 CpG sites (5′-UTR-S_Shelf-cg06573254 and TSS200-Island-cg17647431), two SFXN2 CpG sites (3′-UTR-Open_Sea-cg04774043 and Body-Open_Sea-cg18994254), one SFXN3 CpG site (Body-S_Shelf-cg17858697), nine SFXN5 CpG sites (1stExon; 5′-UTR-Island-cg03856450, Body-Open_Sea-cg04016113, Body-Open_Sea-cg04197631, Body-Open_Sea-cg07558704, Body-Open_Sea-cg08383863, Body-Open_Sea-cg10040131, Body-Open_Sea-cg10588340, Body-Open_Sea-cg17046766, and Body-Open_Sea-cg22830638) were significantly related to the prognosis of BC patients. The miRNAs regulating SFXN1 (has-miR-22-3p, has-miR-140-5p, has-miR-532-5p, and has-miR-582-3p regulating SFXN1) and SFXN2 (has-miR-9-5p, has-miR-34a-5p, has-miR-532-5p, and has-miR-885-5p regulating SFXN2) could be involved in carcinogenesis and influencing the prognosis of BC patients. The detailed studies on mechanisms of SFXN family related to the occurrence, progression, and treatment for BC are required to explore new therapeutic strategies for patients with BC.

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Acknowledgment

The authors thank Shouguang City People’s Hospital for their support.

  1. Funding information: This study was supported by Shouguang City People’s Hospital.

  2. Conflict of interest: All authors declare no conflicts of interest.

  3. Data availability statement: The data shown in this study can be obtained through the corresponding author upon reasonable request.

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Received: 2022-08-30
Revised: 2023-03-02
Accepted: 2023-03-08
Published Online: 2023-04-01

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
  46. The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
  47. Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
  51. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
  52. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
  54. Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
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  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
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  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
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  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
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  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
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  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
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  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
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  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
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  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
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  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
https://doi.org/10.1515/med-2023-0685
Keywords for this article
sideroflexin; breast cancer; biomarkers; prognosis
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
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  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
  7. Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
  17. SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis
  18. Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
  19. Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis
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  26. UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
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  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
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  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
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  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
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  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
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