Startseite High SEC61A1 expression predicts poor outcome of acute myeloid leukemia
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High SEC61A1 expression predicts poor outcome of acute myeloid leukemia

  • Guo Ji , Xiaofei Yang und Jun Li EMAIL logo
Veröffentlicht/Copyright: 27. März 2024
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Open Medicine
Aus der Zeitschrift Open Medicine Band 19 Heft 1

Abstract

The malfunction of SEC61A1 has been linked to several types of cancers, but its role in acute myeloid leukemia (AML) remains poorly understood. In this study, we used a series of bioinformatics analysis techniques, including gene expression profiling and proteomic analysis. Our findings were subsequently validated through a series of in vitro experiments, such as SEC61A1 knockdown in cell lines and RT-qPCR. We discovered a significant up-regulation of SEC61A1 in AML patients compared to healthy controls. AML patients with elevated SEC61A1 expression exhibited reduced overall survival compared to those with lower expression. Moreover, SEC61A1 expression emerged as an independent risk factor for predicting the survival of AML patients undergoing allo-HSCT. Our analysis also revealed an association between high SEC61A1 expression and increased signaling pathways related to cell growth. Our study underscores the importance of SEC61A1 expression as a novel prognostic indicator for predicting survival among AML patients, while also identifying it as a promising therapeutic target.

Keywords: SEC61A1 ; AML; biomarker; prognosis

1 Introduction

Acute myeloid leukemia (AML) stands as a common hematologic malignancy marked by a diverse clonal presence of immature myeloid progenitor cells in both the bone marrow and peripheral blood [1,2], accounting for 80% of newly diagnosed acute leukemia adult patients [1]. Despite noteworthy progress in AML treatment, only 40% of patients below 60 years achieve long-term survival under current therapy [2,3]. Among older patients, survival is significantly worse [3]. Leukemia is classified by two major systems: FAB and WHO. FAB categorizes based on cell types and morphology [4], while WHO considers morphology, immunophenotype, genetics, and clinical features [5]. While FAB was an important first step, WHO offers a more contemporary approach, integrating molecular and immunophenotypic data to enhance therapeutic guidance [5].

Recent advancements in clinical and molecular prognostic markers have markedly enhanced our comprehension of AML biology [5,6]. In addition to traditional markers, the past few years have unveiled novel therapeutic targets and provided insights into identifying individuals who stand to gain the most from specific treatments (such as immune checkpoints [7], macrophage markers [8], chemokine receptors [9], etc.). These breakthroughs are poised to revolutionize the approach to treating individual patients with AML. Therefore, the identification of new molecular markers that can predict survival and serve as treatment targets is of paramount importance.

SEC61A1 protein belongs to SECY/SEC61-alpha family and is located in the endoplasmic reticulum (ER) membrane [10]. It plays a crucial role in the insertion of membrane polypeptides into the ER and is responsible for the retro-translocation of misfolded proteins to the cytosol for degradation [11]. The aberrant function of the SEC61A1 protein has been implicated in various human cancers, including head, lung, prostate, and glioblastoma [12–15], and has been targeted as a therapeutic option in multiple myeloma [10]. A recent study has also reported that SEC61A1 is crucial in mycolactone-dependent apoptosis in AML cells [16]. Nevertheless, the understanding of SEC61A1 expression in AML remains limited.

In this study, we observed that SEC61A1 was highly expressed in AML patients compared to healthy controls. High SEC61A1 expression was associated with poor prognosis in AML and served as a valuable molecular marker for predicting survival.

2 Materials and methods

2.1 Data collection and processing

In this study, we included 151 AML patients derived from The Cancer Genome Atlas (TCGA) dataset [17], with ages ranging from 18 to 88 years. These patients were diagnosed and treated at Washington University between 2001 and 2010 [17]. Following the NCCN guideline, all AML patients underwent the standard induction and consolidation regimen. As stated by the teams, written consents for the study were all available, following the Declaration of Helsinki [17]. Samples of peripheral blood were derived at the time point of diagnosis. Clinical information on survival, baseline characteristics, gene mutation profile, and expression profile could all be downloaded from the TCGA. Additionally, AML-M3 patients were excluded from the study.

Other AML datasets were collected from Gene Expression Omnibus (GEO) (GEO accession numbers: GSE7186 [18], GSE13159 [19], GSE22778 [20], GSE12417 [21]). Written consent for the treatment and the study was also available, as stated by the authors. Microarray data, as well as clinical characteristics, could all be downloaded from the GEO dataset. Proteomic expression data were derived from the Proteomic Data Commons (PDC, National Cancer Institute) (PDC Study Identifier: PDC000477, Project ID: Proteogenomic Translational Research Centers [PTRC]) [22].

2.2 Univariate and multivariate Cox proportional hazards regression model of overall survival with patients’ features (age, sex, mutations, etc.)

The association between survival time with patients’ clinical features was investigated by conducting a univariate and multivariate Cox proportional hazards regression model. Clinical features, including age, sex, white blood cell, platelet counting of peripheral blood, and gene mutation were included in univariate Cox analysis. The hazard ratio (HR) is defined as the ratio of the probability of the event occurring in the exposed group versus the control (non-exposed) group. The inclusion criteria of multi-Cox analysis must meet at least one of the following items: (1) a P-value of univariate Cox analysis result ≤0.20 and (2) clinically recognized that it can have a significant impact on the prognosis. P-value ≤0.05 in multivariate Cox analysis, indicating an independent impact on patient’s survival time. The concordance index (c-index) is a metric to evaluate the predictions made by an algorithm. It is defined as the proportion of concordant pairs divided by the total number of possible evaluation pairs (0.5 < c-index ≤ 0.7, indicating low predictive accuracy; 0.71 ≤ c-index ≤ 0.9, indicating middle predictive accuracy; c-index > 0.9, indicating high predictive accuracy; P-value <0.05, indicating that the hazard model is significant).

2.3 Reverse transcription quantitative PCR (RT‑qPCR)

To extract the total RNA from AML cell lines, we used the Trizol agent (Vazyme Biotech Co., Ltd) following the manufacturer’s protocol. Then HiScript 1st Strand cDNA Synthesis Kit (Vazyme Biotech Co., Ltd) was used to reverse transcribe the extracted mRNA into cDNA. The real-time PCR was performed on a CFX96 TOUCH analysis system (Bio-rad, USA), using ChamQ Universal SYBR qPCR 1Master Mix (Vazyme Biotech Co., Ltd). In this study, we used the following amplification conditions of qPCR: 95°C of pre-denaturation for 30 s, 40 cycles of 95°C of denaturation for 5 s, and 60°C of extension for 30 s. The primer sequences were as follows:

SEC61A1 Forward: 5′- GAAGGAGCAGCAGATGGTGATGAG-3′, Reverse: 5′- GGAAGTCAGCCAGGACCGAGAGAG-3′.

FLT3 Forward: 5′- ACCTCAAGTGCTCGCAGAAGCA-3′, Reverse: 5′-GTTAGCCTTTCTATTCCAGACTCC.

GAPDH Forward: 5′-GCAAATTCCATGGCACCGT-3′, Reverse: 5′- GACTCCACGACGTACTCAGC-3′.

The relative expression levels of the target genes were calculated by the 2−ΔΔCt method.

2.4 Cell lines

The U937 and MV4-11 cell lines were grown in a 5% CO2 atmosphere at 37°C. U937 cells were grown in RPMI-1640 (Gibco, Beijing, China) supplemented with 10% fetal bovine serum (FBS) (Gibco, Beijing, China), MV4-11 cells were grown in IMDM (Gibco, Beijing, China) supplemented with 10% FBS.

2.5 Plasmid construction, lentiviral transduction, and target gene knockdown

Following the manufacturer’s instruction, we constructed lentiviral shRNA plasmids for SEC61A1 by subcloning the shRNA oligos into the lentiviral shRNA vector with an IRES GFP (pLV3ltr-ZsGreen-Puro-U6) (Corues Biotechnology, China). The shRNA oligos design for SEC61A1 is listed in Table S1.

Following the manufacturer’s instructions, 293T cells were transfected with the indicated viral plasmid and psPAX2 and pMD2.G (packaging plasmids) (Corues Biotechnology, China), via Exfect Transfection Reagent (Vazyme Biotech Co., Ltd, China, No. T101-01). After 48 and 72 h post-transfection, viral supernatant was collected and filtered with a 45 μM filter. AML cells were therefore transduced with the resulting lentivirus. HitransG P (KeyGen BioTECH, China) was added to increase the transduction efficiency. After 48 h transduction, 1 µg/mL of puromycin (InvivoGen, CAS.58-58-2) was added into the infected cells for stable expressing cell selection. Via flow cytometry, the efficiency of transduction was monitored by GFP (+) cells, more than 95% of GFP (+) cells were used for knockdown efficiency and further in vitro experiments.

2.6 Bioinformatic analysis of RNA sequencing data

In this study, all bioinformatic analysis was conducted on the R platform and Perl script, R package SVA was used to remove the batch effects and recover the biological signal in the data when integrating different GPL platforms from a common GEO series (GSE22778 contains nine platforms, including GPL8650, GPL8651, GPL8652, GPL8653, GPL8654, GPL10105, GPL10106, GPL10107, GPL10108, n = 185; GSE12417 contains three platforms, including GPL96, GPL97, GPL570, n = 405). R package edgeR was used to conduct the differential expression analysis of the two cohorts (SEC61A1 high and SEC61A1 low cohort). All R scripts used for data analysis in this study are publicly available from GitHub (https://github.com). We used Benjamini and Hochberg’s method to control the false discovery rate. Genes with a fold change over 1.5 (adjusted P-value <0.01) found by edgeR were considered as differentially expressed. Analysis of specific signaling pathways was conducted on Gene Set Enrichment Analysis (GSEA) platform.

This study utilized publicly accessible data from TCGA and GEO databases. These databases contain genomic and expression data from patients worldwide and are anonymized, devoid of directly identifiable personal information.

2.7 Statistical analysis

Data were visualized and analyzed using STATA 16.0 (StataCorp 2019) and Prism 8.0 (GraphPad Prism software). In this study, data were presented as the mean ± SD (normalized distribution) or median (IQR) (skewed distribution). t-test was used to compare two groups, using Prism 8.0 software. Kaplan–Meier method was used to conduct the survival analysis.

  1. Ethical statement: The collection and sharing of data in TCGA and GEO databases adhere to stringent ethical guidelines and regulations, encompassing patient informed consent, privacy protection, and data security. The original data collection received approval from the respective ethics committees, and during the sharing process, any potentially identifying information was removed. The use of data in this study aligns with the data usage policies of TCGA and GEO, posing no potential risks to the privacy and rights of participants. It is explicitly stated that this study does not involve direct experimentation on human or animal subjects; rather, it analyzes publicly available, lawfully obtained genomic and expression data.

3 Results

3.1 Overexpression of SEC61A1 accompanied by the poor prognosis of AML

Two datasets derived from GEO datasets (GSE7186 and GSE13159) were used to compare the expression level of SEC61A1 between AML and healthy cohorts. The results denoted that the expression of SEC61A1 was significantly increased in AML patients, compared to controls (GSE7186, P = 0.0435; GSE13159, P < 0.0001) (Figure 1a and b).

Figure 1 High SEC61A1 expression predicts adverse clinical outcome among AML patients. (a) and (b) Expression level of SEC61A1 in AML are higher, compared with healthy control (samples of GSE7186 and GSE13159 were both derived from bone marrow; *P < 0.05; ***P < 0.0001); (c)–(f) OS analysis of SEC61A1 expression in AML patients, high expression of SEC61A1 predicts poor prognosis in GSE122778 (SEC61A1 high group = 110, SEC61A1 low group = 75), GSE12417 (SEC61A1 high group = 86, SEC61A1 low group = 319), TCGA-non M3 dataset (SEC61A1 high group = 68, SEC61A1 low group = 68), and TCGA-CN AML dataset (SEC61A1 high group = 39, SEC61A1 low group = 38).
Figure 1

High SEC61A1 expression predicts adverse clinical outcome among AML patients. (a) and (b) Expression level of SEC61A1 in AML are higher, compared with healthy control (samples of GSE7186 and GSE13159 were both derived from bone marrow; *P < 0.05; ***P < 0.0001); (c)–(f) OS analysis of SEC61A1 expression in AML patients, high expression of SEC61A1 predicts poor prognosis in GSE122778 (SEC61A1 high group = 110, SEC61A1 low group = 75), GSE12417 (SEC61A1 high group = 86, SEC61A1 low group = 319), TCGA-non M3 dataset (SEC61A1 high group = 68, SEC61A1 low group = 68), and TCGA-CN AML dataset (SEC61A1 high group = 39, SEC61A1 low group = 38).

We further hypothesized that high SEC61A1 expression is associated with poor prognosis in AML patients. Hence, we used three datasets to confirm this finding. The results denoted that high SEC61A1 expression predicts unfavorable prognosis in overall survival in AML (SEC61A1 high vs SEC61A1 low AML cohort, GSE22778, P = 0.0198; GSE12417, P = 0.0177; TCGA [excluding AML-M3], P = 0.0025; TCGA CN-AML, P = 0.0038) (Figure 1c–f).

In addition, the expression of SEC61A1 serves as an indicator for poor OS in non-FLT3 mutant AML patients (TCGA-AML, P = 0.028) (Figure 2a), with SEC61A1 demonstrating notably dismal survival outcomes in the intermediate to high-risk groups (Figure 2b–d). Intriguingly, upon downregulating the expression of SEC61A1 in AML cell lines (Figures S1a, b and S2), we observed a simultaneous reduction in FLT3 expression (Figure S1a and b). Furthermore, we identified a positive correlation between the expression of SEC61A1 and FLT3 in AML (P = 0.0068, R = 0.21) (Figure S3). Further categorizing AML patients based on the expression levels of SEC61A1 and FLT3, we classified them into three groups (SEC61A1 low with FLT3 low, SEC61A1 low and FLT3 high or SEC61A1 high with FLT3 low, and SEC61A1 high with FLT3 high). Notably, the SEC61A1 low with FLT3 low group exhibited the most favorable survival trend among the three, while the SEC61A1 high with FLT3 high group demonstrated the poorest survival outcome (Figure S3).

Figure 2 High SEC61A1 expression predicts adverse clinical outcome among AML patients. (a) OS analysis of SEC61A1 expression in non-FLT3 mutant AML patients, high expression of SEC61A1 predicts poor prognosis. (b)–(d) OS analysis of SEC61A1 expression in favorable cytogenetic risk (b), intermediate risk (c), and poor risk (d).
Figure 2

High SEC61A1 expression predicts adverse clinical outcome among AML patients. (a) OS analysis of SEC61A1 expression in non-FLT3 mutant AML patients, high expression of SEC61A1 predicts poor prognosis. (b)–(d) OS analysis of SEC61A1 expression in favorable cytogenetic risk (b), intermediate risk (c), and poor risk (d).

3.2 Baseline characters of SEC61A1 high and SEC61A1 low AML cohort of TCGA dataset

We conducted a comparison of baseline clinical characteristics and gene mutations between SEC61A1 high and SEC61A1 low AML cohorts using the TCGA dataset. However, no significant differences were observed in age, gender, race, WBC count, platelet count, BM blast percentage, and gene mutations (Table 1). Nevertheless, we discovered that the SEC61A1 high cohort exhibited a higher proportion of FLT3 mutation (P = 0.005) (Table 1).

Table 1

Baseline clinical characteristics of non-M3-AML patients from the TCGA

Characteristic SEC61A1 low SEC61A1 high P
Total 66 67
Cytogenetic risk, n (%) Favorable 8 (6.1%) 8 (6.1%) 0.965
Intermediate 41 (31.3%) 39 (29.8%)
Poor 17 (13%) 18 (13.7%)
Chromosome abnormality, n (%) 8 7 (5.9%) 7 (5.9%) 0.992
Complex over three distinct abnormalities 1 (0.8%) 2 (1.7%)
del(5q)/5q- 2 (1.7%) 3 (2.5%)
del(7q)/7q- 7 (5.9%) 6 (5.1%)
inv(16) 4 (3.4%) 3 (2.5%)
Normal 36 (30.5%) 31 (26.3%)
t(8;21) 3 (2.5%) 4 (3.4%)
t(9;11) 1 (0.8%) 1 (0.8%)
Gender, n (%) Female 36 (27.1%) 25 (18.8%) 0.056
Male 30 (22.6%) 42 (31.6%)
FAB classification, n (%) M0 8 (6.0%) 6 (4.5%) 0.664
M1 14 (10.5%) 21 (15.8%)
M2 18 (13.5%) 20 (15%)
M4 12 (9%) 15 (11.3%)
M5 7 (5.3%) 8 (6%)
M6 0 (0%) 2 (1.5%)
M7 0 (0%) 1 (0.8%)
Not classified 1 (0.8%) 0 (0%)
Race, n (%) Asian 0 (0%) 1 (0.8%) 0.763
Black or African American 5 (3.8%) 6 (4.5%)
White 61 (46.2%) 59 (44.7%)
Age, median (IQR) 54 (41.25, 67) 60 (44.5, 67) 0.216
Platelet counting (×109/L), median (IQR) 52 (28.5, 87) 43 (31, 88) 0.768
WBC counting (×109/L), median (IQR) 20.5 (6, 52.75) 22 (5.5, 46) 0.932
BM blast (%), median (IQR) 46.5 (10, 71) 41 (11.5, 60) 0.659
Hemoglobin (g/L), n (%) 9(9,10) 9(9,11) 0.7695
Treatment “3 + 7” regimen 52 50 0.570
HSCT, n (%) allo-HSCT 35 (26.3%) 26 (19.5%) 0.141
No allo-HSCT 31 (23.3%) 41 (30.8%)
PTPN11 mutant 4 (3%) 2 (1.5%) 0.441
CEBPA mutant 5 (3.8%) 8 (6%) 0.579
TET2 mutant 5 (3.8%) 7 (5.3%) 0.783
FLT3 mutant 11 (8.3%) 27 (20.3%) 0.005
TP53 mutant 5 (3.8%) 6 (4.5%) 0.999
EZH2 mutant 0 (0%) 2 (1.5%) 0.496
NRAS mutant 4 (3%) 3 (2.3%) 0.718
NPM1 mutant 16 (12%) 22 (16.5%) 0.366
DNMT3A mutant 16 (12%) 20 (15%) 0.594
RUNX1 mutant 8 (6%) 6 (4.5%) 0.755
GATA2 mutant 1 (0.8%) 1 (0.8%) 0.999

*Abbreviations: FAB classification: French–American–British classification; allo-HSCT: allogeneic hematopoietic stem cell transplantation; “3 + 7” regimen includes: daunorubicin plus cytarabine.

3.3 Cox proportional hazard model analysis of SEC61A1 expression in CN-AML patients

To gain a better understanding of the correlations between SEC61A1 expression and overall survival, we conducted univariate Cox hazard analysis for TCGA AML patients (excluding M3-AML) based on whether they received allo-HSCT. The included variables were SEC61A1 expression, age, WBC count, BM-blast, hemoglobin, platelet count, cytogenetic risk, and gene mutations (detailed list in Tables S2 and S3, mutation vs. wild type). In patients who did not receive allo-HSCT, the results unveiled that age (HR = 1.029, P = 0.004), intermediate cytogenetic risk (HR = 4.247, P = 0.016), poor cytogenetic risk (HR = 20.555, P < 0.001), TP53 mutation (HR = 3.907, P < 0.001), and DNMT3A mutation (HR = 1.939, P = 0.033) were identified as risk factors. However, other variables showed no statistical significance (Table S2). Meanwhile, for patients who received allo-HSCT, the results indicated that SEC61A1 expression was a significant risk factor (HR = 16.635, P = 0.006) (Table S3).

We further conducted a multivariate Cox hazard analysis for overall survival. Parameters with P values less than 0.2 during univariate Cox hazard analysis were included in the hazard model. The results revealed that poor cytogenetic risk (HR = 18.885, P < 0.001) and FLT3 mutation (HR = 3.0, P = 0.01) were independent risk factors for patients who did not undergo allo-HSCT (Figure 3a) (P < 0.05). Among patients who received allo-HSCT, SEC61A1 expression (HR = 14.787, P = 0.01), JAK3 mutation (HR = 2.293, P = 0.043), CEBPA mutation (HR = 6.611, P = 0.022), and U2AF1 mutation (HR = 2.824, P = 0.013) were identified as independent risk factors. Furthermore, high SEC61A1 expression was found to be the highest risk factor among patients who received allo-HSCT (Figure 3b). These findings indicate that high SEC61A1 expression is an independent risk factor for AML patients udnergoing allo-HSCT.

Figure 3 Forest plot of multivariate COX hazard regression model (TCGA AML-non M3). (a) Forest plot of multivariate COX hazard regression analysis among AML patients without receiving allo-HSCT. (b) Forest plot of multivariate COX hazard regression analysis among AML patients receiving allo-HSCT.
Figure 3

Forest plot of multivariate COX hazard regression model (TCGA AML-non M3). (a) Forest plot of multivariate COX hazard regression analysis among AML patients without receiving allo-HSCT. (b) Forest plot of multivariate COX hazard regression analysis among AML patients receiving allo-HSCT.

3.4 Genome-wide expression profile associated with SEC61A1 expression

To illustrate the underlying molecular mechanism associated with high SEC61A1 expression, we further explored the gene expression profile from the TCGA database. By utilizing R software, we identified 162 differentially expressed genes (DEGs) (SEC61A1 high vs SEC61A1 low AML cohort, |log2FC| > 2, P-value <0.05), including 83 upregulated and 79 downregulated genes (Figure 4a). Notably, EPHA3, MMP7, BIRC7, and ROS1 were found to be upregulated (Figure 4a). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed significant enrichment in the cGMP-PKG signaling pathway and JAK-STAT signaling pathway (Figure 4b). We also performed GSEA analysis to investigate the signaling pathways associated with high SEC61A1 expression. Interestingly, several cell cycle-associated signaling pathways, such as Reactome cell cycle mitotic, Reactome Mphase, and Reactome cell cycle checkpoints, were found to be enriched in the high SEC61A1 expression cohort (Figure 5a–i).

Figure 4 Genome wide expression profile associated with SEC61A1 expression. (a) Volcano plot of DEGs (SEC61A1 high vs SEC61A1 low AML cohort, |log2FC| > 2, P-value <0.05). (b) GO and KEGG analysis result of the DEGs.
Figure 4

Genome wide expression profile associated with SEC61A1 expression. (a) Volcano plot of DEGs (SEC61A1 high vs SEC61A1 low AML cohort, |log2FC| > 2, P-value <0.05). (b) GO and KEGG analysis result of the DEGs.

Figure 5 GSEA analysis result of signaling pathways associated with SEC61A1 expression. (a)–(i) Top eight enriched signaling pathways by GSEA analysis are listed.
Figure 5

GSEA analysis result of signaling pathways associated with SEC61A1 expression. (a)–(i) Top eight enriched signaling pathways by GSEA analysis are listed.

To validate our aforementioned findings, we conducted further investigation into proteomic expression patterns associated with SEC61A1 expression in AML patients using data sourced from the PDC database. A cohort comprising 189 AML patients was included in our analysis. As illustrated in Figure 6a and b, EPHA3, MMP7, BIRC7, and ROS1 exhibited significant upregulation in the SEC61A1 high (n = 95) compared to the SEC61A1 low (n = 94) AML cohort, with |log2FC| > 2 and a P-value <0.05. Additionally, our GO and KEGG analysis revealed pronounced enrichment in the JAK-STAT signaling pathway. Notably, we observed significant enrichment in “leukocyte mediated immunity” and “myeloid leukocyte activation” associated with SEC61A1 expression.

Figure 6 Proteomic analysis result associated with SEC61A1 expression. (a) Heatmap of differentially expressed proteins associated with SEC61A1 expression. (b) Volcano plot of differentially expressed proteins (SEC61A1 high vs SEC61A1 low AML cohort, |log2FC| > 2, P-value <0.05). (c) Top enriched signaling pathways by GO and KEGG analysis are listed.
Figure 6

Proteomic analysis result associated with SEC61A1 expression. (a) Heatmap of differentially expressed proteins associated with SEC61A1 expression. (b) Volcano plot of differentially expressed proteins (SEC61A1 high vs SEC61A1 low AML cohort, |log2FC| > 2, P-value <0.05). (c) Top enriched signaling pathways by GO and KEGG analysis are listed.

4 Discussion

SEC61A1 plays a crucial role in the biogenesis of most secreted and transmembrane proteins [11,23]. This process is fundamental to the proper folding, modification, and transport of proteins destined for secretion or integration into cellular membranes [11,23]. Previous studies have indicated that targeting SEC61A1 enhances sensitivity to anticancer drugs in various hematological malignancies [24–26]. The primary mechanism underlying this effect involves the augmentation of ER stress [26]. Moreover, SEC61A1 has been shown to sensitize AML cells to other drugs by inducing apoptosis [10]. Therefore, investigating the significance of SEC61A1 expression in AML is of great importance.

Traditionally, disease classification relied heavily on pathological and cytological features. However, with a deeper understanding of cancer genetics and proteins, researchers have identified unique molecular markers that aid in the precise categorization of disease subtypes [6]. Furthermore, the emergence of new drugs based on these molecular markers signifies a shift toward individualized therapy. The principles of personalized treatment involve tailoring therapeutic approaches based on a patient’s specific molecular and genetic characteristics [6]. This customization enhances treatment efficacy while minimizing adverse effects on patients.

In this study, we have identified SEC61A1 expression as a novel prognostic marker for AML. Our analysis unveiled a significantly upregulation of SEC61A1 in AML patients compared to healthy controls. Furthermore, higher SEC61A1 expression was found to be associated with shorter overall survival for non-M3 AML patients, especially among those with intermediate/poor risk. Importantly, we demonstrated that SEC61A1 expression was an independent risk factor for OS among AML patients receiving allo-HSCT, suggesting that targeting SEC61A1 may be a valuable strategy for preventing disease relapse after allo-HSCT. Another interesting finding is that we also observed a higher incidence of FLT3 mutations in the SEC61A1 high-expression cohort. FLT3 mutations are relatively common in AML patients, accounting for approximately 30%, and are associated with a poorer prognosis [27]. Most FLT3 proteins undergo unfolding within the ER lumen [28], leading to increased ER stress [29]. Given that SEC61A1 serves as a crucial regulator of ER stress [23], its potential role in maintaining ER homeostasis in AML cells with FLT3 mutations could be significant. Further research is warranted to delve into the intricacies of this relationship and explore additional details in future studies. Above findings have significant implications for the management and treatment of AML patients.

Furthermore, we identified SEC61A1 as a novel prognostic marker for AML and investigated its potential molecular mechanisms. We found that high expression of SEC61A1 was associated with upregulation of EPHA3, MMP7, BIRC7, and ROS1, all of which have been reported as prognostic markers or therapeutic targets in hematological malignancies [30–33]. Furthermore, we explored the correlation between high SEC61A1 expression and several oncogenic signaling pathways. The results revealed that the high SEC61A1 expression was linked to enrichment of the cGMP-PKG and JAK-STAT signaling pathways. It is noteworthy that an overactive cGMP-PKG signaling pathway was reported with anti-apoptotic activity [34], whereas JAK-STAT signaling pathway was reported to be implicated in cell growth and cycle arrest in AML [35]. In addition, our GSEA analysis also supported the association between SEC61A1 expression and cell cycle activity in AML, including “cell cycle M phase, cell cycle G2/M phase, cell cycle checkpoint,” which are indicative of the cell growth dynamics of leukemic cells. Consequently, our proteomic analysis revealed enrichment of the JAK-STAT signaling pathway and cell cycle pathways associated with SEC61A1 expression. These findings serve to affirm the correlation between elevated SEC61A1 expression and activation of oncogenic signaling pathways.

5 Conclusions

In summary, our findings propose SEC61A1 as a promising prognostic marker for assessing the survival outcomes of AML patients. The preliminary insights gleaned from our study regarding this novel marker hold potential for clinical application in the future. We anticipate that our results will catalyze further investigation in this domain, facilitating advancements in AML prognostication and treatment strategies.

Acknowledgements

Not applicable.

  1. Funding information: Medical Education Collaborative Innovation Fund of Jiangsu University (No. JDYY2023135).

  2. Author contributions: X.F.-Y. and J.L. contributed to conception and design of the study. G.J. performed the experiments and statistical analysis. G.J. and J.L. wrote the first draft of the manuscript. All authors contributed to article and approved the submitted version.

  3. Conflict of interest: The authors declare that there are no conflicts of interest.

  4. Data availability statement: The datasets generated and analyzed during the current study are available in the TCGA and GEO repository (https://portal.gdc.cancer.gov/; https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi). Other datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Received: 2023-07-10
Revised: 2024-03-04
Accepted: 2024-03-08
Published Online: 2024-03-27

© 2024 the author(s), published by De Gruyter

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

Artikel in diesem Heft

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  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
https://doi.org/10.1515/med-2024-0944
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SEC61A1; AML; biomarker; prognosis
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Artikel in diesem Heft

  1. Research Articles
  2. EDNRB inhibits the growth and migration of prostate cancer cells by activating the cGMP-PKG pathway
  3. STK11 (LKB1) mutation suppresses ferroptosis in lung adenocarcinoma by facilitating monounsaturated fatty acid synthesis
  4. Association of SOX6 gene polymorphisms with Kashin-Beck disease risk in the Chinese Han population
  5. The pyroptosis-related signature predicts prognosis and influences the tumor immune microenvironment in dedifferentiated liposarcoma
  6. METTL3 attenuates ferroptosis sensitivity in lung cancer via modulating TFRC
  7. Identification and validation of molecular subtypes and prognostic signature for stage I and stage II gastric cancer based on neutrophil extracellular traps
  8. Novel lumbar plexus block versus femoral nerve block for analgesia and motor recovery after total knee arthroplasty
  9. Correlation between ABCB1 and OLIG2 polymorphisms and the severity and prognosis of patients with cerebral infarction
  10. Study on the radiotherapy effect and serum neutral granulocyte lymphocyte ratio and inflammatory factor expression of nasopharyngeal carcinoma
  11. Transcriptome analysis of effects of Tecrl deficiency on cardiometabolic and calcium regulation in cardiac tissue
  12. Aflatoxin B1 induces infertility, fetal deformities, and potential therapies
  13. Serum levels of HMW adiponectin and its receptors are associated with cytokine levels and clinical characteristics in chronic obstructive pulmonary disease
  14. METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients
  15. Understand how machine learning impact lung cancer research from 2010 to 2021: A bibliometric analysis
  16. Pressure ulcers in German hospitals: Analysis of reimbursement and length of stay
  17. Metformin plus L-carnitine enhances brown/beige adipose tissue activity via Nrf2/HO-1 signaling to reduce lipid accumulation and inflammation in murine obesity
  18. Downregulation of carbonic anhydrase IX expression in mouse xenograft nasopharyngeal carcinoma model via doxorubicin nanobubble combined with ultrasound
  19. Feasibility of 3-dimensional printed models in simulated training and teaching of transcatheter aortic valve replacement
  20. miR-335-3p improves type II diabetes mellitus by IGF-1 regulating macrophage polarization
  21. The analyses of human MCPH1 DNA repair machinery and genetic variations
  22. Activation of Piezo1 increases the sensitivity of breast cancer to hyperthermia therapy
  23. Comprehensive analysis based on the disulfidptosis-related genes identifies hub genes and immune infiltration for pancreatic adenocarcinoma
  24. Changes of serum CA125 and PGE2 before and after high-intensity focused ultrasound combined with GnRH-a in treatment of patients with adenomyosis
  25. The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis
  26. Development and validation of a novel model to predict pulmonary embolism in cardiology suspected patients: A 10-year retrospective analysis
  27. Downregulation of lncRNA XLOC_032768 in diabetic patients predicts the occurrence of diabetic nephropathy
  28. Circ_0051428 targeting miR-885-3p/MMP2 axis enhances the malignancy of cervical cancer
  29. Effectiveness of ginkgo diterpene lactone meglumine on cognitive function in patients with acute ischemic stroke
  30. The construction of a novel prognostic prediction model for glioma based on GWAS-identified prognostic-related risk loci
  31. Evaluating the impact of childhood BMI on the risk of coronavirus disease 2019: A Mendelian randomization study
  32. Lactate dehydrogenase to albumin ratio is associated with in-hospital mortality in patients with acute heart failure: Data from the MIMIC-III database
  33. CD36-mediated podocyte lipotoxicity promotes foot process effacement
  34. Efficacy of etonogestrel subcutaneous implants versus the levonorgestrel-releasing intrauterine system in the conservative treatment of adenomyosis
  35. FLRT2 mediates chondrogenesis of nasal septal cartilage and mandibular condyle cartilage
  36. Challenges in treating primary immune thrombocytopenia patients undergoing COVID-19 vaccination: A retrospective study
  37. Let-7 family regulates HaCaT cell proliferation and apoptosis via the ΔNp63/PI3K/AKT pathway
  38. Phospholipid transfer protein ameliorates sepsis-induced cardiac dysfunction through NLRP3 inflammasome inhibition
  39. Postoperative cognitive dysfunction in elderly patients with colorectal cancer: A randomized controlled study comparing goal-directed and conventional fluid therapy
  40. Long-pulsed ultrasound-mediated microbubble thrombolysis in a rat model of microvascular obstruction
  41. High SEC61A1 expression predicts poor outcome of acute myeloid leukemia
  42. Comparison of polymerase chain reaction and next-generation sequencing with conventional urine culture for the diagnosis of urinary tract infections: A meta-analysis
  43. Secreted frizzled-related protein 5 protects against renal fibrosis by inhibiting Wnt/β-catenin pathway
  44. Pan-cancer and single-cell analysis of actin cytoskeleton genes related to disulfidptosis
  45. Overexpression of miR-532-5p restrains oxidative stress response of chondrocytes in nontraumatic osteonecrosis of the femoral head by inhibiting ABL1
  46. Autologous liver transplantation for unresectable hepatobiliary malignancies in enhanced recovery after surgery model
  47. Clinical analysis of incomplete rupture of the uterus secondary to previous cesarean section
  48. Abnormal sleep duration is associated with sarcopenia in older Chinese people: A large retrospective cross-sectional study
  49. No genetic causality between obesity and benign paroxysmal vertigo: A two-sample Mendelian randomization study
  50. Identification and validation of autophagy-related genes in SSc
  51. Long non-coding RNA SRA1 suppresses radiotherapy resistance in esophageal squamous cell carcinoma by modulating glycolytic reprogramming
  52. Evaluation of quality of life in patients with schizophrenia: An inpatient social welfare institution-based cross-sectional study
  53. The possible role of oxidative stress marker glutathione in the assessment of cognitive impairment in multiple sclerosis
  54. Compilation of a self-management assessment scale for postoperative patients with aortic dissection
  55. Left atrial appendage closure in conjunction with radiofrequency ablation: Effects on left atrial functioning in patients with paroxysmal atrial fibrillation
  56. Effect of anterior femoral cortical notch grade on postoperative function and complications during TKA surgery: A multicenter, retrospective study
  57. Clinical characteristics and assessment of risk factors in patients with influenza A-induced severe pneumonia after the prevalence of SARS-CoV-2
  58. Analgesia nociception index is an indicator of laparoscopic trocar insertion-induced transient nociceptive stimuli
  59. High STAT4 expression correlates with poor prognosis in acute myeloid leukemia and facilitates disease progression by upregulating VEGFA expression
  60. Factors influencing cardiovascular system-related post-COVID-19 sequelae: A single-center cohort study
  61. HOXD10 regulates intestinal permeability and inhibits inflammation of dextran sulfate sodium-induced ulcerative colitis through the inactivation of the Rho/ROCK/MMPs axis
  62. Mesenchymal stem cell-derived exosomal miR-26a induces ferroptosis, suppresses hepatic stellate cell activation, and ameliorates liver fibrosis by modulating SLC7A11
  63. Endovascular thrombectomy versus intravenous thrombolysis for primary distal, medium vessel occlusion in acute ischemic stroke
  64. ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis
  65. Prognostic value of EIF5A2 in solid tumors: A meta-analysis and bioinformatics analysis
  66. The role of enhanced expression of Cx43 in patients with ulcerative colitis
  67. Choosing a COVID-19 vaccination site might be driven by anxiety and body vigilance
  68. Role of ICAM-1 in triple-negative breast cancer
  69. Cost-effectiveness of ambroxol in the treatment of Gaucher disease type 2
  70. HLA-DRB5 promotes immune thrombocytopenia via activating CD8+ T cells
  71. Efficacy and factors of myofascial release therapy combined with electrical and magnetic stimulation in the treatment of chronic pelvic pain syndrome
  72. Efficacy of tacrolimus monotherapy in primary membranous nephropathy
  73. Mechanisms of Tripterygium wilfordii Hook F on treating rheumatoid arthritis explored by network pharmacology analysis and molecular docking
  74. FBXO45 levels regulated ferroptosis renal tubular epithelial cells in a model of diabetic nephropathy by PLK1
  75. Optimizing anesthesia strategies to NSCLC patients in VATS procedures: Insights from drug requirements and patient recovery patterns
  76. Alpha-lipoic acid upregulates the PPARγ/NRF2/GPX4 signal pathway to inhibit ferroptosis in the pathogenesis of unexplained recurrent pregnancy loss
  77. Correlation between fat-soluble vitamin levels and inflammatory factors in paediatric community-acquired pneumonia: A prospective study
  78. CD1d affects the proliferation, migration, and apoptosis of human papillary thyroid carcinoma TPC-1 cells via regulating MAPK/NF-κB signaling pathway
  79. miR-let-7a inhibits sympathetic nerve remodeling after myocardial infarction by downregulating the expression of nerve growth factor
  80. Immune response analysis of solid organ transplantation recipients inoculated with inactivated COVID-19 vaccine: A retrospective analysis
  81. The H2Valdien derivatives regulate the epithelial–mesenchymal transition of hepatoma carcinoma cells through the Hedgehog signaling pathway
  82. Clinical efficacy of dexamethasone combined with isoniazid in the treatment of tuberculous meningitis and its effect on peripheral blood T cell subsets
  83. Comparison of short-segment and long-segment fixation in treatment of degenerative scoliosis and analysis of factors associated with adjacent spondylolisthesis
  84. Lycopene inhibits pyroptosis of endothelial progenitor cells induced by ox-LDL through the AMPK/mTOR/NLRP3 pathway
  85. Methylation regulation for FUNDC1 stability in childhood leukemia was up-regulated and facilitates metastasis and reduces ferroptosis of leukemia through mitochondrial damage by FBXL2
  86. Correlation of single-fiber electromyography studies and functional status in patients with amyotrophic lateral sclerosis
  87. Risk factors of postoperative airway obstruction complications in children with oral floor mass
  88. Expression levels and clinical significance of serum miR-19a/CCL20 in patients with acute cerebral infarction
  89. Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022
  90. Evaluating anemia in HIV-infected patients using chest CT
  91. Ponticulus posticus and skeletal malocclusion: A pilot study in a Southern Italian pre-orthodontic court
  92. Causal association of circulating immune cells and lymphoma: A Mendelian randomization study
  93. Assessment of the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals on treating renal fibrosis: A systematic review and meta-analysis
  94. Comprehensive landscape of integrator complex subunits and their association with prognosis and tumor microenvironment in gastric cancer
  95. New target-HMGCR inhibitors for the treatment of primary sclerosing cholangitis: A drug Mendelian randomization study
  96. Population pharmacokinetics of meropenem in critically ill patients
  97. Comparison of the ability of newly inflammatory markers to predict complicated appendicitis
  98. Comparative morphology of the cruciate ligaments: A radiological study
  99. Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
  100. Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study
  101. SHP-1 mediates cigarette smoke extract-induced epithelial–mesenchymal transformation and inflammation in 16HBE cells
  102. Acute hyper-hypoxia accelerates the development of depression in mice via the IL-6/PGC1α/MFN2 signaling pathway
  103. The GJB3 correlates with the prognosis, immune cell infiltration, and therapeutic responses in lung adenocarcinoma
  104. Physical fitness and blood parameters outcomes of breast cancer survivor in a low-intensity circuit resistance exercise program
  105. Exploring anesthetic-induced gene expression changes and immune cell dynamics in atrial tissue post-coronary artery bypass graft surgery
  106. Empagliflozin improves aortic injury in obese mice by regulating fatty acid metabolism
  107. Analysis of the risk factors of the radiation-induced encephalopathy in nasopharyngeal carcinoma: A retrospective cohort study
  108. Reproductive outcomes in women with BRCA 1/2 germline mutations: A retrospective observational study and literature review
  109. Evaluation of upper airway ultrasonographic measurements in predicting difficult intubation: A cross-section of the Turkish population
  110. Prognostic and diagnostic value of circulating IGFBP2 in pancreatic cancer
  111. Postural stability after operative reconstruction of the AFTL in chronic ankle instability comparing three different surgical techniques
  112. Research trends related to emergence agitation in the post-anaesthesia care unit from 2001 to 2023: A bibliometric analysis
  113. Frequency and clinicopathological correlation of gastrointestinal polyps: A six-year single center experience
  114. ACSL4 mediates inflammatory bowel disease and contributes to LPS-induced intestinal epithelial cell dysfunction by activating ferroptosis and inflammation
  115. Affibody-based molecular probe 99mTc-(HE)3ZHER2:V2 for non-invasive HER2 detection in ovarian and breast cancer xenografts
  116. Effectiveness of nutritional support for clinical outcomes in gastric cancer patients: A meta-analysis of randomized controlled trials
  117. The relationship between IFN-γ, IL-10, IL-6 cytokines, and severity of the condition with serum zinc and Fe in children infected with Mycoplasma pneumoniae
  118. Paraquat disrupts the blood–brain barrier by increasing IL-6 expression and oxidative stress through the activation of PI3K/AKT signaling pathway
  119. Sleep quality associate with the increased prevalence of cognitive impairment in coronary artery disease patients: A retrospective case–control study
  120. Dioscin protects against chronic prostatitis through the TLR4/NF-κB pathway
  121. Association of polymorphisms in FBN1, MYH11, and TGF-β signaling-related genes with susceptibility of sporadic thoracic aortic aneurysm and dissection in the Zhejiang Han population
  122. Application value of multi-parameter magnetic resonance image-transrectal ultrasound cognitive fusion in prostate biopsy
  123. Laboratory variables‐based artificial neural network models for predicting fatty liver disease: A retrospective study
  124. Decreased BIRC5-206 promotes epithelial–mesenchymal transition in nasopharyngeal carcinoma through sponging miR-145-5p
  125. Sepsis induces the cardiomyocyte apoptosis and cardiac dysfunction through activation of YAP1/Serpine1/caspase-3 pathway
  126. Assessment of iron metabolism and iron deficiency in incident patients on incident continuous ambulatory peritoneal dialysis
  127. Tibial periosteum flap combined with autologous bone grafting in the treatment of Gustilo-IIIB/IIIC open tibial fractures
  128. The application of intravenous general anesthesia under nasopharyngeal airway assisted ventilation undergoing ureteroscopic holmium laser lithotripsy: A prospective, single-center, controlled trial
  129. Long intergenic noncoding RNA for IGF2BP2 stability suppresses gastric cancer cell apoptosis by inhibiting the maturation of microRNA-34a
  130. Role of FOXM1 and AURKB in regulating keratinocyte function in psoriasis
  131. Parental control attitudes over their pre-school children’s diet
  132. The role of auto-HSCT in extranodal natural killer/T cell lymphoma
  133. Significance of negative cervical cytology and positive HPV in the diagnosis of cervical lesions by colposcopy
  134. Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin
  135. ADAR1 plays a protective role in proximal tubular cells under high glucose conditions by attenuating the PI3K/AKT/mTOR signaling pathway
  136. The risk of cancer among insulin glargine users in Lithuania: A retrospective population-based study
  137. The unusual location of primary hydatid cyst: A case series study
  138. Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation
  139. Obesity and risk of placenta accreta spectrum: A meta-analysis
  140. Shikonin alleviates asthma phenotypes in mice via an airway epithelial STAT3-dependent mechanism
  141. NSUN6 and HTR7 disturbed the stability of carotid atherosclerotic plaques by regulating the immune responses of macrophages
  142. The effect of COVID-19 lockdown on admission rates in Maternity Hospital
  143. Temporal muscle thickness is not a prognostic predictor in patients with high-grade glioma, an experience at two centers in China
  144. Luteolin alleviates cerebral ischemia/reperfusion injury by regulating cell pyroptosis
  145. Therapeutic role of respiratory exercise in patients with tuberculous pleurisy
  146. Effects of CFTR-ENaC on spinal cord edema after spinal cord injury
  147. Irisin-regulated lncRNAs and their potential regulatory functions in chondrogenic differentiation of human mesenchymal stem cells
  148. DMD mutations in pediatric patients with phenotypes of Duchenne/Becker muscular dystrophy
  149. Combination of C-reactive protein and fibrinogen-to-albumin ratio as a novel predictor of all-cause mortality in heart failure patients
  150. Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease
  151. Ferroptosis-related prognostic model of mantle cell lymphoma
  152. Observation of choking reaction and other related indexes in elderly painless fiberoptic bronchoscopy with transnasal high-flow humidification oxygen therapy
  153. A bibliometric analysis of Prader-Willi syndrome from 2002 to 2022
  154. The causal effects of childhood sunburn occasions on melanoma: A univariable and multivariable Mendelian randomization study
  155. Oxidative stress regulates glycogen synthase kinase-3 in lymphocytes of diabetes mellitus patients complicated with cerebral infarction
  156. Role of COX6C and NDUFB3 in septic shock and stroke
  157. Trends in disease burden of type 2 diabetes, stroke, and hypertensive heart disease attributable to high BMI in China: 1990–2019
  158. Purinergic P2X7 receptor mediates hyperoxia-induced injury in pulmonary microvascular endothelial cells via NLRP3-mediated pyroptotic pathway
  159. Investigating the role of oviductal mucosa–endometrial co-culture in modulating factors relevant to embryo implantation
  160. Analgesic effect of external oblique intercostal block in laparoscopic cholecystectomy: A retrospective study
  161. Elevated serum miR-142-5p correlates with ischemic lesions and both NSE and S100β in ischemic stroke patients
  162. Correlation between the mechanism of arteriopathy in IgA nephropathy and blood stasis syndrome: A cohort study
  163. Risk factors for progressive kyphosis after percutaneous kyphoplasty in osteoporotic vertebral compression fracture
  164. Predictive role of neuron-specific enolase and S100-β in early neurological deterioration and unfavorable prognosis in patients with ischemic stroke
  165. The potential risk factors of postoperative cognitive dysfunction for endovascular therapy in acute ischemic stroke with general anesthesia
  166. Fluoxetine inhibited RANKL-induced osteoclastic differentiation in vitro
  167. Detection of serum FOXM1 and IGF2 in patients with ARDS and their correlation with disease and prognosis
  168. Rhein promotes skin wound healing by activating the PI3K/AKT signaling pathway
  169. Differences in mortality risk by levels of physical activity among persons with disabilities in South Korea
  170. Review Articles
  171. Cutaneous signs of selected cardiovascular disorders: A narrative review
  172. XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis
  173. A narrative review on adverse drug reactions of COVID-19 treatments on the kidney
  174. Emerging role and function of SPDL1 in human health and diseases
  175. Adverse reactions of piperacillin: A literature review of case reports
  176. Molecular mechanism and intervention measures of microvascular complications in diabetes
  177. Regulation of mesenchymal stem cell differentiation by autophagy
  178. Molecular landscape of borderline ovarian tumours: A systematic review
  179. Advances in synthetic lethality modalities for glioblastoma multiforme
  180. Investigating hormesis, aging, and neurodegeneration: From bench to clinics
  181. Frankincense: A neuronutrient to approach Parkinson’s disease treatment
  182. Sox9: A potential regulator of cancer stem cells in osteosarcoma
  183. Early detection of cardiovascular risk markers through non-invasive ultrasound methodologies in periodontitis patients
  184. Advanced neuroimaging and criminal interrogation in lie detection
  185. Maternal factors for neural tube defects in offspring: An umbrella review
  186. The chemoprotective hormetic effects of rosmarinic acid
  187. CBD’s potential impact on Parkinson’s disease: An updated overview
  188. Progress in cytokine research for ARDS: A comprehensive review
  189. Utilizing reactive oxygen species-scavenging nanoparticles for targeting oxidative stress in the treatment of ischemic stroke: A review
  190. NRXN1-related disorders, attempt to better define clinical assessment
  191. Lidocaine infusion for the treatment of complex regional pain syndrome: Case series and literature review
  192. Trends and future directions of autophagy in osteosarcoma: A bibliometric analysis
  193. Iron in ventricular remodeling and aneurysms post-myocardial infarction
  194. Case Reports
  195. Sirolimus potentiated angioedema: A case report and review of the literature
  196. Identification of mixed anaerobic infections after inguinal hernia repair based on metagenomic next-generation sequencing: A case report
  197. Successful treatment with bortezomib in combination with dexamethasone in a middle-aged male with idiopathic multicentric Castleman’s disease: A case report
  198. Complete heart block associated with hepatitis A infection in a female child with fatal outcome
  199. Elevation of D-dimer in eosinophilic gastrointestinal diseases in the absence of venous thrombosis: A case series and literature review
  200. Four years of natural progressive course: A rare case report of juvenile Xp11.2 translocations renal cell carcinoma with TFE3 gene fusion
  201. Advancing prenatal diagnosis: Echocardiographic detection of Scimitar syndrome in China – A case series
  202. Outcomes and complications of hemodialysis in patients with renal cancer following bilateral nephrectomy
  203. Anti-HMGCR myopathy mimicking facioscapulohumeral muscular dystrophy
  204. Recurrent opportunistic infections in a HIV-negative patient with combined C6 and NFKB1 mutations: A case report, pedigree analysis, and literature review
  205. Letter to the Editor
  206. Letter to the Editor: Total parenteral nutrition-induced Wernicke’s encephalopathy after oncologic gastrointestinal surgery
  207. Erratum
  208. Erratum to “Bladder-embedded ectopic intrauterine device with calculus”
  209. Retraction
  210. Retraction of “XRCC1 and hOGG1 polymorphisms and endometrial carcinoma: A meta-analysis”
  211. Corrigendum
  212. Corrigendum to “Investigating hormesis, aging, and neurodegeneration: From bench to clinics”
  213. Corrigendum to “Frankincense: A neuronutrient to approach Parkinson’s disease treatment”
  214. Special Issue The evolving saga of RNAs from bench to bedside - Part II
  215. Machine-learning-based prediction of a diagnostic model using autophagy-related genes based on RNA sequencing for patients with papillary thyroid carcinoma
  216. Unlocking the future of hepatocellular carcinoma treatment: A comprehensive analysis of disulfidptosis-related lncRNAs for prognosis and drug screening
  217. Elevated mRNA level indicates FSIP1 promotes EMT and gastric cancer progression by regulating fibroblasts in tumor microenvironment
  218. Special Issue Advancements in oncology: bridging clinical and experimental research - Part I
  219. Ultrasound-guided transperineal vs transrectal prostate biopsy: A meta-analysis of diagnostic accuracy and complication rates
  220. Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer
  221. SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins
  222. MARK1 suppress malignant progression of hepatocellular carcinoma and improves sorafenib resistance through negatively regulating POTEE
  223. Analysis of postoperative complications in bladder cancer patients
  224. Carboplatin combined with arsenic trioxide versus carboplatin combined with docetaxel treatment for LACC: A randomized, open-label, phase II clinical study
  225. Special Issue Exploring the biological mechanism of human diseases based on MultiOmics Technology - Part I
  226. Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma
  227. Identification of signatures associated with microsatellite instability and immune characteristics to predict the prognostic risk of colon cancer
  228. Single-cell analysis identified key macrophage subpopulations associated with atherosclerosis
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Heruntergeladen am 5.11.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2024-0944/html
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