Startseite Medizin Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator
Artikel Open Access

Immune landscape of hepatocellular carcinoma: The central role of TP53-inducible glycolysis and apoptosis regulator

  • Lingbing Qiu , Tianyi Ma , Yunmiao Guo EMAIL logo und Jugao Chen EMAIL logo
Veröffentlicht/Copyright: 30. Juli 2024
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Open Medicine
Aus der Zeitschrift Open Medicine Band 19 Heft 1

Abstract

Objective

This study aims to address the substantive issue of lacking reliable prognostic biomarkers in hepatocellular carcinoma (HCC) by investigating the relationship between TP53-inducible glycolysis and apoptosis regulator (TIGAR) and HCC prognosis using The Cancer Genome Atlas database.

Methods

(1) Integrated statistical analyses, including logistic regression, Wilcoxon signed-rank test, and Kruskal–Wallis test, were conducted to explore the association between TIGAR expression and clinical–pathological features of HCC. (2) The Kaplan–Meier method combined with univariate and multivariate Cox regression models underscored TIGAR as a prognostic factor in HCC. (3) Gene set enrichment analysis (GSEA) revealed key pathways associated with TIGAR, while single-sample gene set enrichment analysis (ssGSEA) determined its relevance to cancer immune infiltration.

Results

(1) Elevated TIGAR expression was significantly correlated with decreased survival outcomes in HCC patients. (2) GSEA highlighted the significant link between TIGAR and humoral immunity. (3) ssGSEA revealed a positive correlation between TIGAR expression and infiltration of Th1 and Th2 cells and a negative correlation with Th17 cell infiltration.

Conclusion

TIGAR, as a potential prognostic biomarker for HCC, holds significant value in immune infiltration. Understanding the role of TIGAR could contribute to improved prognostic predictions and personalized treatment strategies for HCC patients.

Keywords: TP53-inducible glycolysis and apoptosis regulator; hepatocellular carcinoma; the cancer genome atlas; prognostic biomarker; gene set enrichment analysis; single-sample gene set enrichment analysis

1 Introduction

Hepatocellular carcinoma (HCC) stands as the predominant histologic type of liver cancer, ranking as the third leading cause of cancer-related mortality globally [1]. Particularly prevalent in regions like Asia and Africa, chronic exposure to the hepatitis B virus remains its primary risk factor [2,3]. Despite notable therapeutic advancements in recent decades, our understanding of the molecular mechanisms driving its onset and progression remains substantially incomplete [4]. Furthermore, existing screening methodologies for HCC, including serum alpha-fetoprotein (AFP), ultrasonography, and CT scanning, often fail to detect the disease in its early stages. Consequently, most patients receive a diagnosis at an advanced stage, leading to dismal prognoses with a 5-year survival rate that does not exceed 20% [5]. This pressing scenario underscores an urgent need to identify viable biomarkers capable of facilitating early detection and targeted treatment for HCC patients.

Tumor suppressor TP53-inducible glycolysis and apoptosis regulator (TIGAR), a downstream target of P53, plays a pivotal role in apoptosis and autophagy regulation [6,7]. TIGAR inhibits glycolysis and the upstream genes of reactive oxygen species (ROS) responses, thereby modulating autophagy. This process can be disrupted by excessive nicotinamide adenine dinucleotide phosphate supplementation [7]. Moreover, TIGAR mediates glucose metabolism, regulating intracellular ROS levels to promote cell survival and DNA damage repair, highlighting its significance in these crucial cellular processes [8,9,10]. Studies have also hinted at TIGAR’s potential involvement in the regulation of cell cycle, proliferation, invasion, and metastasis-related proteins in tumor cells [11]. Noteworthy is the significant elevation of TIGAR expression observed in various human tumors such as colon cancer, breast cancer, and glioblastoma, suggesting its potential as a valuable tool in early tumor diagnosis and precise treatment [12,13,14]. However, the precise mechanisms governing HCC development and progression via TIGAR remain inadequately explored.

Therefore, our study aimed to bridge this knowledge gap, shedding light on the role of TIGAR in HCC and its prognostic implications. Our findings, particularly the association between elevated TIGAR expression and poorer survival rates in HCC patients, as well as the correlation between TIGAR and humoral immunity, have significantly expanded our understanding of the molecular landscape of HCC. Additionally, the discovery of distinct correlations between TIGAR expression and the levels of infiltrating Th1, Th2, and Th17 cells opens avenues for further investigation into the immunological mechanisms at play in HCC. From a clinical perspective, our results could revolutionize patient care. If TIGAR expression is confirmed as a reliable prognostic marker in HCC, it could be integrated into predictive models, enabling clinicians to forecast patient outcomes accurately and customize therapeutic strategies. Thus, our research signifies a significant stride toward more personalized and effective treatments for HCC patients.

2 Materials and methods

2.1 Data acquisition

We procured RNA-sequencing data (HTseq-counts) along with pertinent clinical data for 424 TCGA (The Cancer Genome Atlas)-LIHC samples from the TCGA database (https://portal.gdc.cancer.gov/). This dataset includes 50 samples from normal adjacent tissues and 374 from HCC tissues. Our analysis made use of the transcripts per million (TPM) read data from the same 424 subjects, with both normal and tumor tissues represented in this patient group.

The process encompassed the conversion of the TPM format from FPKM (fragments per kilobase per million), the application of log 2 transformation, and then using the resultant clinical and RNA-seq data for our research objectives. It should be noted that all the information deployed in this study was accessible to the public.

2.2 Differentially expressed gene (DEG) analysis

We employed the R package DEseq2 to distinguish DEGs among groups that exhibited distinct TIGAR expression levels, applying a cutoff of |log fold change (log FC)| ≥ 1.5 and a false discovery rate (FDR) of less than 0.05. To facilitate visualization of the differential expression analyses’ outcomes, we made use of R packages, namely EnhancedVolcano and pheatmap.

2.3 Enrichment analysis

We executed gene set enrichment analysis (GSEA) and gene ontology (GO) functional enrichment scrutiny using the R package known as Cluster Analyzer. To graphically represent the results, we employed the ggplot2 package in R. We set an FDR less than 0.25 and p.adjust <0.05 as the threshold for significant enrichment. For GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, we used C5.mf.v7.2.symbols.gmt (GO) and C2.Cp.v7.2.symbols.gmt (Curated) as the reference gene sets, respectively. The categories considered in the GO analysis spanned cellular component (CC), molecular function (MF), and biological process (BP).

2.4 Protein–protein interaction (PPI) network

We constructed a PPI network of proteins co-expressed with TIGAR using the online database STRING (http://string-db.org). To do this, we fetched interacting proteins that showed an interaction score exceeding 0.4 and a PPI enrichment P-value <0.001. STRING is a digital platform dedicated to enabling the discovery of gene interactions. The procured TIGAR-associated proteins were subsequently imported into the Cluster Profiler 3.14.3 software, which facilitated the visualization of their mutual interaction patterns.

In addition, we carried out a differential examination of individual genes linked with TIGAR and scrutinized the co-expressed genes via enrichment analysis and KEGG pathway assessments. The output of these analyses was visually represented using the ggplot2 package.

2.5 Immune infiltration analysis

We harnessed the GSVA package [1.34.0] within the R environment [3.6.3] to execute single-sample gene set enrichment analysis (ssGSEA) on TIGAR, enabling a systematic review of immune infiltrates mentioned in extant literature. We explored the connection between TIGAR and signature genes associated with 24 distinct immune cell types.

To distinguish the differences in immune cell infiltration between TIGAR high-expression and low-expression groups, we employed Wilcoxon rank-sum tests. For the purpose of assessing the relationship between TIGAR gene expression and the density of tumor-infiltrating immune cells, we utilized mRNA sequencing data drawn from the TCGA Tumor Immune Estimation Resource (TIMER2.0) database (http://timer.cistrome.org/).

To establish the correlation between TIGAR and the 24 types of immune cells, we deployed the Spearman Correlation analysis. We used TIMER 2.0 to investigate the relationship between TIGAR expression and immune infiltration. This tool enables the estimation of immune infiltration based on the expression profiles provided by users using the CIBERSORT algorithm. The results were consistent with those obtained using the ssGSEA algorithm.

2.6 Statistical analysis

We processed statistical data obtained from TCGA utilizing the R package (version 3.6.3). The comparative analysis of TIGAR expression levels between HCC and normal groups was performed employing the Wilcoxon signed-rank test and Wilcoxon rank-sum test. The influence of Clinicopathological factors on TIGAR expression was evaluated through univariate logistic regression and Fisher’s exact tests.

We performed the Receiver Operating Characteristic (ROC) analysis of TIGAR using the Proc package (version 1.17.0.1). The area under the curve (AUC) was considered significant for our study if it ranged between 0.5 and 1. An AUC value closer to 1 symbolizes superior diagnostic efficacy, with a result above 0.9 signifying elevated accuracy. For all the statistical tests performed, a P-value <0.05 was regarded as significant.

  1. Ethics approval and consent to participate: This article does not contain any studies with human participants or animals performed by any of the authors.

3 Results

3.1 Differential expression analysis of TIGAR in other cancers and HCC

Gene expression analysis using the RNA-seq database revealed higher TIGAR mRNA expression in tumor samples compared to the corresponding normal tissues (p < 0.05) based on the Wilcoxon rank sum test (Figure 1a). These findings demonstrate that TIGAR expression is upregulated in cancer tissues. We investigated the expression of TIGAR in 50 normal samples and 374 HCC tumor samples derived from the TCGA dataset. Additionally, the volcano plots of TIGAR differentially expressed RNAs and the significantly high expression of TIGAR in HCC samples (p < 0.05) provide further support for our results (Figure 1b and c). Finally, the heat map illustrates 25 TIGAR-related genes (Figure 1d).

Figure 1 Differential expression levels of TIGAR in different malignancies and TIGAR-related DEGs. (a) Increased or decreased TIGAR of different cancers compared with normal tissues in the TCGA database. (b) The volcano plot of differentially expressed mRNAs. The red dots represent mRNAs with significantly high expression levels, blue dots represent mRNAs with significantly low expression levels, and gray dots indicate mRNAs with no significant differential expression. The selection criteria for significantly expressed mRNAs were set at |log fold change (logFC)| ≥ 1.5 and p < 0.05. (c) TIGAR expression level in case-matched HCC and normal tissues. (d) Volcano plots of the DEGs and heat map showing the 25 related genes (*** p < 0.01).
Figure 1

Differential expression levels of TIGAR in different malignancies and TIGAR-related DEGs. (a) Increased or decreased TIGAR of different cancers compared with normal tissues in the TCGA database. (b) The volcano plot of differentially expressed mRNAs. The red dots represent mRNAs with significantly high expression levels, blue dots represent mRNAs with significantly low expression levels, and gray dots indicate mRNAs with no significant differential expression. The selection criteria for significantly expressed mRNAs were set at |log fold change (logFC)| ≥ 1.5 and p < 0.05. (c) TIGAR expression level in case-matched HCC and normal tissues. (d) Volcano plots of the DEGs and heat map showing the 25 related genes (*** p < 0.01).

3.2 Functional enrichment analysis of DEGs with TIGAR

The findings of the GO analysis revealed that TIGAR-related DEGs significantly regulate the CC, BP, and MF. Specifically, there were notable changes in the BP of TIGAR, which were associated with the humoral immune response mediated by circulating immunoglobulin, immunoglobulin-mediated immune response, lymphocyte-mediated immunity, and immune response-activating cell surface receptor signaling pathway, among others. The CC annotations involved immunoglobulin complex and circulating immunoglobulin complex, while the MF analysis indicated antigen binding (Figure 2a, Table 1). Furthermore, the PPI network of TIGAR demonstrated its potential co-expression proteins in TIGAR-related DEGs, as shown in Figure 2b. Specifically, TIGAR was found to be correlated with 21 genes such as TP53, TPI1, SCO2, and C12orf5. These genes consist of the Phosphofructokinase B Family (PFKFB1, PFKFB2, PFKFB3, and PFKFB4) and the Hexokinase Family (HK1, HK2, and HK3). Notably, TP53 and TPI1 have been linked to the inhibition of CD8 T cell infiltration and HCC metastasis [15,16]. Additionally, TCF19 and TP53 are involved in regulating TIGAR and SCO2 transcription in HCC, which is pivotal for mitochondrial energy metabolism and stress adaptation [17].

Figure 2 GO and KEGG enrichment analysis of TIGAR in HCC. (a) BP, CCs, MF enrichment, and KEGG related to TIGAR-related genes. (b) A network of TIGAR (TP53 protein) and 20 potential co-interaction proteins. (c)–(f) Results of enrichment analysis from GSEA.
Figure 2

GO and KEGG enrichment analysis of TIGAR in HCC. (a) BP, CCs, MF enrichment, and KEGG related to TIGAR-related genes. (b) A network of TIGAR (TP53 protein) and 20 potential co-interaction proteins. (c)–(f) Results of enrichment analysis from GSEA.

Table 1

TIGAR-related genes related to BP, CCs, MF enrichment, and KEGG

Ontology ID Description p-value p. adjust Z score
BP GO:0002455 Humoral immune response mediated by circulating immunoglobulin 5.51 × 10−46 9.32 × 10−43 7.211
BP GO:0016064 Immunoglobulin-mediated immune response 7.71 × 10−38 5.86 × 10−35 7.280
BP GO:0002449 Lymphocyte-mediated immunity 1.28 × 10−29 4.81 × 10−27 7.483
BP GO:0002429 Immune response-activating cell surface receptor signaling pathway 4.57 × 10−27 1.40 × 10−24 7.810
BP GO:0006911 Phagocytosis, engulfment 4.93 × 10−26 1.39 × 10−23 5.745
BP GO:0002920 Regulation of humoral immune response 4.39 × 10−24 8.72 × 10−22 5.745
BP GO:0050853 B-cell receptor signaling pathway 1.70 × 10−23 3.03 × 10−21 5.657
BP GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis 2.07 × 10−22 3.33 × 10−20 5.657
BP GO:0050871 Positive regulation of B-cell activation 4.19 × 10−22 6.15 × 10−20 5.657
BP GO:0002377 Immunoglobulin production 9.45 × 10−22 1.28 × 10−19 6.000
BP GO:0002440 Production of molecular mediator of immune response 8.63 × 10−17 8.83 × 10−15 6.083
BP GO:0038093 Fc receptor signaling pathway 7.78 × 10−16 7.74 × 10−14 5.745
BP GO:0030324 Lung development 4.87 × 10−06 3.22 × 10−04 4.000
CC GO:0019814 Immunoglobulin complex 1.41 × 10−64 4.91 × 10−62 8.124
CC GO:0042571 Immunoglobulin complex, circulating 2.21 × 10−34 3.86 × 10−32 5.745
MF GO:0003823 Antigen binding 9.90 × 10−41 5.32 × 10−38 7.000
KEGG hsa04971 Gastric acid secretion 1.31 × 10−04 1.68 × 10−02 2.828
KEGG hsa04974 Protein digestion and absorption 1.04 × 10−03 4.50 × 10−2 2.828

The GSEA analysis results for the GO term revealed a positive correlation between high TIGAR levels and signaling processes related to the immunoglobulin complex, antigen binding, and immunoglobulin receptor binding (Figure 2c). On the other hand, processes such as aromatase activity, structural constituent of ribosome, and cotranslational protein targeting to the membrane displayed a negative correlation with elevated TIGAR levels (Figure 2e).

Additionally, the curated gene set examination indicated a positive correlation between high TIGAR levels and the p53 signaling pathway, DNA replication, natural killer (NK) cell-mediated cytotoxicity, and antigen processing and presentation (Figure 2d). In contrast, focal adhesion, hypertrophic cardiomyopathy, hypertrophic cardiomyopathy extracellular matrix receptor interaction, drug metabolism cytochrome p450, and tyrosine metabolism were found to be negatively correlated with elevated TIGAR levels (Figure 2f). These observations propose a central enrichment of pathways regulating immune infiltrates and a robust association with TIGAR single-gene expression.

To deepen our understanding of TIGAR’s biological functions, we undertook GSEA on the variance between datasets reflecting low and high TIGAR expression. The aim was to identify GO and the GO term associated with TIGAR. The analysis of differentially expressed TIGAR genes unveiled a total of 678 KEGG pathways that showed noteworthy differential enrichment from the c5.all.v7.2.symbols.gmt (GO) dataset (FDR <0.05, adjusted p < 0.05). The KEGG pathways and GO term signatures most significantly enriched, based on their Normalized Enrichment Scores (NES), are presented in Table 2. The analysis revealed that TIGAR-related genes are primarily involved in BPs, such as the immune globulin complex, antigen binding, and humoral immune response mediated by circulating immunoglobulin. Additionally, these genes play a crucial role in pathways, including the p53 signaling pathway, DNA replication, drug metabolism cytochrome P450, and amino acid metabolism. Research has shown that diosgenin saponin exerts an effective role in HCC by modulating TIGAR-mediated cell apoptosis, autophagy, and DNA damage [18].

Table 2

Signaling pathways most significantly associated with TIGAR expression

Name Description NES p-value p. adjust
Positive GO term GO_IMMUNOGLOBULIN_COMPLEX 3.394 0.001 0.009
GO_ANTIGEN_BINDING 3.150 0.001 0.009
GO_HUMORAL_IMMUNE_RESPONSE_MEDIATED_BY_CIRCULATING_IMMUNOGLOBULIN 3.093 0.001 0.009
GO_IMMUNOGLOBULIN_COMPLEX_CIRCULATING 3.073 0.001 0.009
GO_IMMUNOGLOBULIN_RECEPTOR_BINDING 3.042 0.001 0.009
Negative GO term GO_AROMATASE_ACTIVITY −2.636 0.003 0.013
GO_STRUCTURAL_CONSTITUENT_OF_RIBOSOME −3.369 0.017 0.044
GO_CYTOSOLIC_RIBOSOME −3.395 0.009 0.028
GO_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_NONSENSE_MEDIATED_DECAY −3.397 0.011 0.031
GO_COTRANSLATIONAL_PROTEIN_TARGETING_TO_MEMBRANE −3.586 0.008 0.025
Positive KEGG term KEGG_P53_SIGNALING_PATHWAY 1.982 0.003 0.029
KEGG_DNA_REPLICATION 2.130 0.003 0.029
KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION 1.884 0.003 0.029
KEGG_ANTIGEN_PROCESSING_AND_PRESENTATION 1.884 0.003 0.029
KEGG_NATURAL_KILLER_CELL_MEDIATED_CYTOTOXICITY 1.803 0.003 0.029
Negative KEGG term KEGG_FOCAL_ADHESION −2.929 0.001 0.029
KEGG_HYPERTROPHIC_CARDIOMYOPATHY_HCM −1.663 0.005 0.038
KEGG_ECM_RECEPTOR_INTERACTION −1.731 0.003 0.029
KEGG_DRUG_METABOLISM_CYTOCHROME_P450 −1.724 0.003 0.029
KEGG_TYROSINE_METABOLISM −2.858 0.002 0.029

3.3 Relationship between TIGAR expression and immune infiltration

Through the application of the Spearman correlation method, we examined the relationship between TIGAR expression levels and immune infiltration in the tumor microenvironment, using ssGSEA for our analysis. Interestingly, Th2 cells were observed to be significantly elevated in the high TIGAR expression cohort (p < 0.001), demonstrating a distinct positive correlation with TIGAR expression (Spearman R = 0.325, p < 0.001) (Figure 3a and c). In contrast, Th17 cells presented significantly lower levels in the high TIGAR expression cohort (p < 0.001) and exhibited a notable negative correlation with TIGAR expression (Spearman R = −0.171, p < 0.001) (Figure 3b and d).

Figure 3 The results of analysis between TIGAR expression and immune infiltration. (a) The positive correlation between TIGAR expression and Th2 cells. (b) The negative correlation between TIGAR expression and Th17 cells. (c) Th2 cells’ infiltration level in different TIGAR expression groups. (d) Th17 cells’ infiltration level in different TIGAR expression groups. (e) and (f) Correlation between TIGAR expression level and the relative abundances of 24 immune cells.
Figure 3

The results of analysis between TIGAR expression and immune infiltration. (a) The positive correlation between TIGAR expression and Th2 cells. (b) The negative correlation between TIGAR expression and Th17 cells. (c) Th2 cells’ infiltration level in different TIGAR expression groups. (d) Th17 cells’ infiltration level in different TIGAR expression groups. (e) and (f) Correlation between TIGAR expression level and the relative abundances of 24 immune cells.

To visually represent the correlation between TIGAR expression and the diversity of immune cells, we utilized lollipop plots. The derived results highlighted a positive association between TIGAR and various immune cells, including activated DC (aDC), B cells, immature DC (iDC), Macrophages, Mast cells, Neutrophils, NK CD56bright cells, NK cells, T cells, T helper cells, T central memory (Tcm), T effector memory (Tem), T follicular helper (Tfh), and Th1 cells. In contrast, Th17 cells exhibited a negative relationship with TIGAR (Figure 3e). Furthermore, a heat map provided visual evidence of the reciprocal relationship between TIGAR gene expression and the diverse types of tumor-infiltrating immune cells (Figure 3f). These findings emphasize the pivotal role that TIGAR undertakes in facilitating immune infiltration within HCC.

3.4 Associations between TIGAR expression and clinicopathological variables

Table 3 summarizes the correlation between TIGAR levels and clinicopathological characteristics, such as normal vs tumor, pathological N stage (N), pathological stage, pathologic stage, gender, age, neoplasm type, and tumor stage of LIHC patients (n = 374) from the TCGA-LIHC database. The expression of TIGAR shows significant differences among different patient characteristic groups, as illustrated in Figure 4a–h. Specifically, TIGAR exhibits higher expression in tumor samples and N0 and N1 samples compared to normal samples. Moreover, it is upregulated in Alive and Dead samples, as well as in Stage I, Stage II, pathologic stage, and Stage III and Stage IV samples. Additionally, TIGAR expression is elevated in T1, T2, and T3 and T4 samples. White patients show higher TIGAR expression compared to Asian patients. Furthermore, in samples with albumin levels <3.5 g/dl and albumin levels ≥ 3.5 g/dl, TIGAR expression is higher than in normal samples. Similarly, TIGAR expression is elevated in samples with AFP levels ≤400 ng/ml and AFP levels >400 ng/ml compared to normal samples.

Table 3

Clinicopathological characteristics of LIHC patients

Characteristics Total (N) Odds ratio (OR) p value
T stage (T2 & T3 & T4 vs T1) 371 1.309 (0.871–1.972) 0.195
N stage (N1 vs N0) 258 0.939 (0.111–7.923) 0.950
M stage (M1 vs M0) 272 1.094 (0.130–9.224) 0.929
Pathologic stage (Stage III & Stage IV vs Stage I & Stage II) 350 1.414 (0.875–2.297) 0.159
Gender (male vs female) 374 1.130 (0.733–1.745) 0.581
Race (Black or African American & White vs Asian) 362 1.825 (1.202–2.784) 0.005
Age (>60 vs ≤60) 373 1.056 (0.703–1.586) 0.793
Weight (>70 vs ≤70) 346 1.517 (0.993–2.323) 0.055
Height (≥170 vs <170) 341 1.712 (1.110–2.654) 0.016
BMI (>25 vs ≤25) 337 1.221 (0.796–1.875) 0.361
AFP (ng/ml) (>400 vs ≤400) 280 0.744 (0.422–1.300) 0.302
Albumin (g/dl) (≥3.5 vs <3.5) 300 1.027 (0.599–1.764) 0.923
Prothrombin time (>4 vs ≤4) 297 1.772 (1.075–2.944) 0.026
Figure 4 Association between TIGAR expression and different clinicopathological characteristics. (a) TIGAR expression between normal and tumor; (b) association between TIGAR expression and the N stage of HCC; (c) OS event; (d) the pathologic stage; (e) T stage; (f) race; (g) albumin; and (h) AFP.
Figure 4

Association between TIGAR expression and different clinicopathological characteristics. (a) TIGAR expression between normal and tumor; (b) association between TIGAR expression and the N stage of HCC; (c) OS event; (d) the pathologic stage; (e) T stage; (f) race; (g) albumin; and (h) AFP.

Our findings highlight that TIGAR expression is elevated in LIHC tissues, with high TIGAR levels strongly correlating with LIHC progression and metastasis. Notably, logistic regression analysis underscored a significant association between TIGAR expression and the patient’s race (p = 0.005) (Table 4).

Table 4

TIGAR expression correlated with clinicopathological characteristics analyzed by logistic regression

Characteristics Total (N) Odds ratio (OR) p value
T stage (T2 & T3 & T4 vs T1) 371 1.309 (0.871–1.972) 0.195
N stage (N1 vs N0) 258 0.939 (0.111–7.923) 0.950
M stage (M1 vs M0) 272 1.094 (0.130–9.224) 0.929
Pathologic stage (Stage III & Stage IV vs Stage I & Stage II) 350 1.414 (0.875–2.297) 0.159
Gender (male vs female) 374 1.130 (0.733–1.745) 0.581
Race (Black or African American & White vs Asian) 362 1.825 (1.202–2.784) 0.005
Age (>60 vs ≤60) 373 1.056 (0.703–1.586) 0.793
Weight (>70 vs ≤70) 346 1.517 (0.993–2.323) 0.055
Height (≥170 vs <170) 341 1.712 (1.110–2.654) 0.016
BMI (>25 vs ≤25) 337 1.221 (0.796–1.875) 0.361
AFP (ng/ml) (>400 vs ≤400) 280 0.744 (0.422–1.300) 0.302
Albumin (g/dl) (≥ 3.5 vs <3.5) 300 1.027 (0.599–1.764) 0.923
Prothrombin time (>4 vs ≤4) 297 1.772 (1.075–2.944) 0.026

Univariate Cox regression analysis revealed that factors such as T stage (p < 0.001), M stage (p = 0.017), pathologic stage (p < 0.001), tumor presence (p < 0.001), and TIGAR expression (p < 0.001) are linked to poor prognosis for HCC (Figure 5a). Conversely, multivariate Cox regression identified tumor presence as a factor associated with worsened HCC prognosis (p = 0.004) (Table 5).

Figure 5 The prognostic value of TIGAR in LIHC. (a) Univariate Cox regression visualized in the forest plot. (b) Diagnostic ROC curve of TIGAR. (c) Time-dependent ROC curve of TIGAR. (d) A nomogram for predicting the probability of 1-, 3-, and 5-year OS for LIHC patients. (e) TIGAR expression distribution and survival status.
Figure 5

The prognostic value of TIGAR in LIHC. (a) Univariate Cox regression visualized in the forest plot. (b) Diagnostic ROC curve of TIGAR. (c) Time-dependent ROC curve of TIGAR. (d) A nomogram for predicting the probability of 1-, 3-, and 5-year OS for LIHC patients. (e) TIGAR expression distribution and survival status.

Table 5

Univariate and multivariate analyses of clinical pathological parameters in LIHC patients

Characteristics Total (N) Univariate analysis Multivariate analysis
Hazard ratio (95% CI) p value Hazard ratio (95% CI) p value
T stage 370
T1 & T2 277 Reference
T3 & T4 93 2.598 (1.826–3.697) <0.001 1.586 (0.215–11.686) 0.651
N stage 258
N0 254 Reference
N1 4 2.029 (0.497–8.281) 0.324
M stage 272
M0 268 Reference
M1 4 4.077 (1.281–12.973) 0.017 1.202 (0.286–5.052) 0.802
Gender 373
Female 121 Reference
Male 252 0.793 (0.557–1.130) 0.200
Age 373
≤ 60 177 Reference
>60 196 1.205 (0.850–1.708) 0.295
Race 361
Asian 159 Reference
White 185 1.323 (0.909–1.928) 0.144
Black or African American 17 1.585 (0.675–3.725) 0.290
Pathologic stage 349
Stage I & Stage II 259 Reference
Stage III & Stage IV 90 2.504 (1.727–3.631) <0.001 1.452 (0.198–10.673) 0.714
Tumor status 354
Tumor free 202 Reference
With tumor 152 2.317 (1.590–3.376) <0.001 1.975 (1.239–3.148) 0.004
TIGAR 373 1.505 (1.172–1.933) 0.001 1.355 (0.994–1.847) 0.054

Bold values represent the difference was statistically significant, less than 0.05.

In the univariate Cox analysis, the pathologic stage (p < 0.001), T stage (p < 0.001), and TIGAR expression were examined as prognostic indicators for overall survival (OS). After adjusting for covariates, the presence of a tumor (p = 0.004) emerged as a significant predictor of OS (Table 5). Given that the p-value for the multivariable analysis of TIGAR is 0.054, TIGAR demonstrates a marginal association with survival rates after adjusting for covariates. Intriguingly, the ROC analysis of TIGAR further validated the diagnostic precision of the score (AUC = 0.714, 90% CI: 0.645–0.783) (Figure 5b). Furthermore, we performed a reliable time-dependent ROC analysis to assess TIGAR’s time-dependent accuracy in predicting OS over 1, 2, and 3 years (Figure 5c). Finally, a nomogram was generated, facilitating quantitative prognosis prediction for LIHC patients by incorporating TIGAR and other independent clinical risk factors (Figure 5d).

Figure 5e demonstrates the distribution of TIGAR expression, the survival status of HCC patients, and the corresponding expression profiles of TIGAR. The findings indicate that increased TIGAR expression correlates with a worse prognosis. The gray and orange dots, respectively, denote surviving and deceased HCC patients. Importantly, the line on the upper left corresponds to the low-risk score group exhibiting low TIGAR expression, while the orange line on the right represents the high-risk score group showing high TIGAR expression. As the risk score in HCC patients escalates, the quantity of orange dots progressively increases, suggesting that high-risk group patients have lower survival rates and a higher likelihood of mortality.

The prognostic value of TIGAR in HCC OS was evaluated using the Kaplan–Meier (K–M) survival curve, generated by the “survminer” R package. HCC patients were divided into high and low-expression groups based on the median value of TIGAR expression. The analysis revealed that the group with high TIGAR expression was significantly associated with poorer OS (HR = 1.54 (1.08–2.18), p = 0.016) (Figure 6a). Moreover, increased TIGAR expression was linked with poorer OS in various subgroups, including the T1 subgroup of T stage (HR = 1.83 (1.01–3.34), p = 0.047), stage N subgroup of pathologic stage (HR = 1.77 (1.14–2.76), p = 0.011), Stages I and II of pathologic stage (HR = 1.85 (1.13–3.03, p = 0.014)), G1 and G2 and G3 subgroup of histologic grade (HR = 1.65 (1.15–2.37), p = 0.007), and the R0 subgroup of tumor status (HR = 1.48 (1.02–2.17), p = 0.041) among others (Figure 6b–l).

Figure 6 The prognostic value of TIGAR in the different subgroups. (a) The prognostic value of TIGAR in OS of HCC. (b)–(k) High expression of TIGAR associated with worse OS in different subgroups. (l) The prognostic value of TIGAR in DSS of HCC.
Figure 6

The prognostic value of TIGAR in the different subgroups. (a) The prognostic value of TIGAR in OS of HCC. (b)–(k) High expression of TIGAR associated with worse OS in different subgroups. (l) The prognostic value of TIGAR in DSS of HCC.

4 Discussion

In the past decade, substantial progress has been achieved in the clinical diagnosis and treatment of HCC. This progress includes advancements in therapies such as surgical resection, chemotherapy, radiotherapy, molecule-targeted therapy, interventional therapy, immunotherapy, and traditional Chinese medicine [19,20]. Despite these multifaceted approaches, the prognosis for HCC patients remains dismal, with a 5-year survival rate of less than 20%, primarily due to a high rate of recurrence following treatment [21]. Previous studies have documented prognostic biomarkers for HCC, such as ALDOB, which is considered a prognostic biomarker for early diagnosis of HCC. Several inflammation-associated gene expression characteristics, including CD274 (PD-L1), CD8A, LAG3, and STAT1, are associated with improved objective response rates (p = 0.05) and OS (p = 0.01). These genes hold predictive value as biomarkers for HCC [22]. However, the predictive value of these biomarkers requires further confirmation in larger phase III trials. Consequently, there is an urgent need to identify potential biomarkers to improve the prognosis of HCC patients.

Abnormal tumor cell metabolism has been widely acknowledged in the field of oncology and has become a focal point of research. The concept traces back to 1924 when Warburg discovered that tumor cells could evade normal apoptosis processes through aberrant glucose metabolism. This abnormal metabolism, known as the Warburg effect, allows tumor cells to enhance proliferation and migration by generating ATP through aerobic glycolysis instead of the tricarboxylic acid cycle. The glucose metabolism status of tumor cells is closely linked to their survival and anti-apoptotic abilities. Notably, the TIGAR gene is a key player in tumor metabolism regulation. TIGAR, a downstream target of p53, regulates mitochondrial respiration and inhibits glycolysis, reducing ROS and increasing GSH levels, thus preventing tumor cell apoptosis [23]. TIGAR achieves this by modulating cellular redox levels, lowering F-2 and 6-P levels, or enhancing HK2 activity, allowing cells to evade apoptosis caused by ROS under stress. Moreover, TIGAR’s role in regulating autophagy in response to metabolic stress conditions is not fully understood. TIGAR expression is regulated through both p53-dependent and p53-independent mechanisms, altering the tumor metabolic microenvironment and promoting DNA repair and cell proliferation [24]. As an ROS restriction protein, TIGAR is highly expressed in tumor cells, exerting antioxidant effects by regulating NADPH production via the pentose phosphate pathway. This reduces apoptosis induced by oxidative damage and promotes tumor cell proliferation and metastasis [25]. The relationship between TIGAR and various solid tumors, including primary colon carcinoma, invasive breast carcinoma, lung cancer, nasopharyngeal carcinoma, gastric cancer, renal cell carcinoma, and prostate carcinoma, has been studied. High TIGAR expression is associated with aggressive tumor behavior and poor patient prognosis [26,27,28].

Tumor markers have become a key and effective method for early clinical diagnosis, and the combined detection of multiple markers can compensate for the limitations of single-marker testing, offering new strategies for the prognosis and auxiliary diagnosis of liver cancer [29]. In our research, we observed a significant upregulation of TIGAR expression in HCC tissue samples. This elevated TIGAR expression was associated with unfavorable survival outcomes in HCC patients, consistent with earlier studies [26,27,28]. Notably, the high-risk group exhibited substantially higher levels of TIGAR expression compared to the low-risk group. Utilizing a Cox regression model, we demonstrated that TIGAR, along with factors such as T stage, M stage, pathologic stage, and tumor presence, correlated with a poor prognosis for HCC. These findings suggest a pivotal role for TIGAR in HCC progression, urging further exploration of its functional dynamics within the disease. The findings presented above offer a theoretical basis for early detection of HCC. Monitoring the expression levels of TIGAR at different stages of pathological features can facilitate the development of more precise treatment strategies.

To delve deeper into TIGAR’s molecular mechanisms, we constructed co-expression networks associated with TIGAR in the context of HCC. Our analysis revealed that TIGAR co-expressed genes were predominantly involved in diverse processes, including the immunoglobulin complex, antigen binding, immunoglobulin receptor binding signaling, the p53 signaling pathway, DNA replication, NK cell-mediated cytotoxicity, and antigen processing and presentation. This intricate network underscores the multifaceted role of TIGAR in HCC, warranting comprehensive investigations to decode its functional dynamics within the disease.

Moreover, the significance of the tumor microenvironment in HCC progression has been increasingly acknowledged. The liver’s tumor microenvironment comprises various components, including tumor cells, tumor-infiltrating lymphocytes, tumor-associated macrophages, neutrophils, cancer-associated fibroblasts, myeloid-derived suppressor cells, dendritic cells, extracellular matrix, and other matrix-associated molecules [30]. The diverse distribution of tumor-infiltrating immune cells and the expression of immune checkpoint-related genes in HCC underscore the pivotal role of the tumor microenvironment in HCC progression.

CD8+ cytotoxic T lymphocytes play a crucial role in efficiently eliminating tumor cells through the secretion of cytokines associated with prognosis [31]. Conversely, regulatory T cells, a suppressive subset of CD4+ T lymphocytes, can inhibit immune responses initiated by CD8+ cytotoxic T lymphocytes, thereby promoting tumor evasion [32]. B cells exert anti-tumor effects by producing antibodies and acting as antigen-presenting cells to stimulate T-cell responses [33].

Upon activation by pharmaceuticals or other treatments, these lymphocytes have the potential to suppress HCC growth. Tumor-associated neutrophils can attract macrophages and regulatory T cells to tumor sites by releasing cytokines, thereby facilitating tumor progression and metastasis [34]. Certain molecular and CCs in the tumor microenvironment can induce functional abnormalities in dendritic cells, enabling tumor cells to evade immune detection [35]. In HCC, cancer-associated fibroblasts significantly contribute to tumor cell communication by activating various signaling pathways and expressing cytokines, establishing a microenvironment conducive to tumor cell growth [36].

Tumor-associated macrophages are classified into two phenotypes: the tumor-inhibiting M1 and tumor-promoting M2 [37]. M1-like macrophages can counteract HCC progression by modulating the tumor microenvironment, whereas M2-like macrophages can promote HCC cell proliferation and invasion by activating the TLR4/STAT3 signaling pathway [38,39]. Previous studies have reported that TIGAR increases during the formation of macrophage foam cells and atherosclerosis. Knocking down TIGAR significantly promotes lipid accumulation in macrophages [40]. Research has shown that desitabin downregulates TIGAR, inducing apoptosis and autophagy in myeloid leukemia cells, affecting cell metabolism, apoptosis, and immunity [41]. However, the relationship between TIGAR and macrophage polarization in HCC tumors has not been studied. In future research, we will continue to investigate this aspect further, aiming to explore its impact on the progression of HCC.

Our findings shed light on the complex interplay between TIGAR expression and immune cell infiltration within the tumor microenvironment, providing valuable insights into the mechanisms underlying HCC development and progression.

Our study revealed a compelling association between high TIGAR expression and diminished OS rates in HCC patients. Through GSEA, we have established a close relationship between TIGAR and humoral immunity, indicating the pivotal involvement of TIGAR in modulating the body’s antibody-mediated immune responses.

Furthermore, our analysis uncovered intriguing correlations between TIGAR expression and various immune cell populations. Specifically, Th17 cells, a subset of CD4+ T helper cells known for secreting inflammatory cytokines that promote tumorigenesis, exhibited significantly lower infiltration levels in the TIGAR high-expression group. This decrease in Th17 cell infiltration was notably correlated with the elevated expression of TIGAR, suggesting a negative regulatory role of TIGAR in Th17 cell-mediated inflammation within the HCC microenvironment. However, the effect size of Th17 is not too large. The biology that links TIGAR and Th17 needs further investigation.

Additionally, our study highlighted the intricate relationships between TIGAR and other immune cells, including aDCs, B cells, immature DCs, macrophages, mast cells, neutrophils, NK CD56 bright cells, NK cells, T cells, Tcm, Tem cells, and Tfh cells. These correlations underscore the multifaceted immunomodulatory roles played by TIGAR in shaping the immune landscape of HCC.

Macrophages, essential components of the immune system, play a crucial role in phagocytosing cellular fragments and pathogens. However, the polarization of macrophages may suppress the host’s immune response, potentially contributing to tumor development. In our analysis, we observed a complex interplay between TIGAR expression and macrophage polarization (Figure 3e and f), highlighting a possible mechanism through which TIGAR could influence immune responses within the HCC microenvironment.

Moreover, our study emphasized the pivotal role of NK cells, which are essential for initiating nonspecific immune responses and eliminating target cells, including various tumor cells. Elevated TIGAR expression levels were associated with altered NK cell activity, further implicating TIGAR in the dysregulation of immune surveillance against HCC cells. During the GO and GSEA analysis, several reasons may account for the lack of enrichment of glucose metabolism-related genes in the GO and GSEA entries. One potential explanation could be the threshold utilized for screening DEGs. Employing highly stringent thresholds may result in the exclusion of glucose metabolism-related genes, leading to their absence in the GO and GSEA analyses. Another possible reason could be attributed to the selection of the dataset, which may also elucidate the absence of significant glucose metabolism features in the analysis.

While our bioinformatics analysis has provided valuable insights, it is essential to acknowledge the limitations inherent in theoretical studies. To validate our findings and unravel the underlying mechanisms, further in vivo and in vitro experimental investigations are imperative. These experiments will not only corroborate our bioinformatics results but also offer a deeper understanding of the intricate molecular pathways through which TIGAR influences immune infiltration and HCC progression.

5 Conclusions

In summary, our study illuminates the intricate roles of TIGAR in HCC progression, emphasizing its impact on immune cell infiltration and overall patient survival. The correlations established between TIGAR expression and various immune cell populations underscore the complexity of immune regulation within the HCC microenvironment. While our bioinformatics analysis forms a solid foundation, future experimental studies are warranted to decipher the precise mechanisms through which TIGAR modulates immune responses and influences HCC development.

tel: +86-13570597379

  1. Funding information: We gratefully acknowledge the support of the Shenzhen Science and Technology Program (JCYJ20190806151610947).

  2. Author contributions: LBQ analyzed the data and wrote the original draft. LBQ and JGC conceived and designed the study. LBQ, TYM, and JGC carried out the literature review and conceptualization. YMG and JGC managed the correspondence. All authors read and approved the final manuscript.

  3. Conflict of interest: The authors declare no conflict of interest.

  4. Data availability statement: The data underlying this article will be shared on reasonable request to the corresponding author.

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Received: 2023-11-21
Revised: 2024-06-10
Accepted: 2024-06-26
Published Online: 2024-07-30

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

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

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  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
https://doi.org/10.1515/med-2024-0999
Schlagwörter für diesen Artikel
TP53-inducible glycolysis and apoptosis regulator; hepatocellular carcinoma; the cancer genome atlas; prognostic biomarker; gene set enrichment analysis; single-sample gene set enrichment analysis
Creative Commons
BY 4.0

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 25.12.2025 von https://www.degruyterbrill.com/document/doi/10.1515/med-2024-0999/html
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