Expression and prognostic roles of PRDXs gene family in hepatocellular carcinoma.
Ontology highlight
ABSTRACT: Background
As the fourth leading cause of cancer-related death in the world, the therapeutic effect and 5-year overall survival of hepatocellular carcinoma (HCC) are not optimistic. Previous researches indicated that the disorder of PRDXs was related to the occurrence and development of cancers.Methods
In this study, PRDXs were found in various tumor cell lines by CCLE database analysis. The analysis results of UALCAN, HCCDB and Human Protein Atlas databases showed the expression of PRDXs mRNA and protein in HCC tissues was dysregulated. Besides, UALCAN was used to assess the correlations between PRDXs mRNA as well as methylation levels and clinical characterization.Results
High expression of PRDX1 or low expression of PRDX2/3 suggested poor prognosis for HCC patients which was demonstrated by Kaplan-Meier Plotter. The genetic alterations and biological interaction network of PRDXs in HCC samples were obtained from c-Bioportal. In addition, LinkedOmics was employed to analyze PRDXs related differentially expressed genes, and on this basis, enrichment of KEGG pathway and miRNAs targets of PRDXs were conducted. The results indicated that these genes were involved in several canonical pathways and certain amino acid metabolism, some of which may effect on the progression of HCC.Conclusions
In conclusion, the disordered expression of some PRDX family members was associated with the prognosis of HCC patients, suggesting that these PRDX family members may become new molecular targets for the treatment and prognosis prediction of HCC.
SUBMITTER: Xu M
PROVIDER: S-EPMC7995729 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundDishevelled (DVL) family members are crucial to Wnt-induced signaling transduction, and their expression is highly correlated with the progression of multiple malignant cancers. However, the expression profiles and exact prognostic values of DVLs in hepatocellular carcinoma (HCC) have not been explored until now.MethodsThe expression of DVL isoforms was assessed using the Oncomine, HCCDB and UALCAN databases. The prognostic roles of DVLs were further evaluated using the GEPIA database. The relationship between the expression of DVLs and immune infiltration of HCC was investigated using the Timer and ImmuCellAI tools. Furthermore, protein-protein interaction (PPI) networks were built and enrichment analyses were conducted.ResultsWe found that the expression levels of DVL2 (OMIM accession number: 602151) and DVL3 (OMIM accession number: 601368) were upregulated in HCC tissues as revealed by the Oncomine and HCCDB databases. Additionally, the expression of DVLs tended to be associated with advanced clinical features in the UALCAN database. Prognostic analysis revealed that the expression levels of DVL1 (OMIM accession number: 601365) and DVL3 were remarkably associated with a poor prognosis in HCC patients. The results also revealed that the DVL expression level was correlated with the infiltration levels of multiple immune cells. By constructing the PPI network and enrichment analyses, the DVL1-3 gene was identified to interact with 20 key genes and participate in several pathways.ConclusionIn summary, DVL2 and DVL3 are highly expressed in HCC, and DVL1 and DVL3 are related to a poor prognosis, which might be used as candidate targets for targeted therapy and reliable prognostic biomarkers in HCC.
| S-EPMC7507050 | biostudies-literature
Project description:BackgroundSignal transducer and activator of transcription (STAT) proteins are well-known transcription factors that play an important role in the progression of cancer. However, the association between STAT family genes and hepatocellular carcinoma (HCC) remains unclear. This study investigates the expression level, the prognostic value and the potential mechanism of STAT family genes in HCC.MethodsData from 365 HCC patients in The Cancer Genome Atlas (TCGA) database and 241 HCC patients in the Gene Expression Omnibus (GEO) database were used to investigate the diagnostic and prognostic values of STAT genes by survival analysis and nomogram. Gene set enrichment analysis (GSEA) was used to investigate the potential mechanism of the STAT genes in the development of HCC.ResultsOur results showed that STAT4/5B mRNA expression levels in HCC tissues were lower than those in normal tissues. Importantly, our results indicated that high expression of STAT5A, STAT5B and STAT6 was associated with better overall survival in HCC patients. Joint effects analysis of STAT5A, STAT5B and STAT6 suggested that the prognosis difference for any combination of genes was more significant than that for any individual gene. Then, we developed a risk score model could predict HCC prognosis and the nomogram visualized gene expression and clinical factors of probability for HCC prognosis. The ROC and calibration curves showed good performance in survival prediction in both the TCGA and the GEO databases. GSEA suggested that high expression of STAT5A, STAT5B and STAT6 were involved in immune-related biological processes, drug metabolism cytochrome P450, JAK-STAT signalling pathway, and PPAR signalling pathways.ConclusionOur data suggest that STAT5A, STAT5B and STAT6 expression may be potential prognostic markers of HCC and, in combination, have a better predictive value for HCC prognosis.
| S-EPMC6731967 | biostudies-literature
Project description:Nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)C and NLRX family proteins play a key role in the innate immune response. The relationship between these proteins and hepatocellular carcinoma (HCC) remains unclear. This study investigated the prognostic significance of NLRC and NLRX family protein levels in HCC patients. Data from 360 HCC patients in The Cancer Genome Atlas database and 231 patients in the Gene Expression Omnibus database were analyzed. Kaplan-Meier analysis and a Cox regression model were used to determine median survival time (MST) and overall and recurrence-free survival by calculating the hazard ratio (HR) and 95% confidence interval (CI). High NOD2 and low NLRX1 expression in tumor tissue was associated with short MST (P = 0.012 and 0.014, respectively). A joint-effects analysis of NOD2 and NLRX1 combined revealed that groups III and IV had reduced risk of death from HCC as compared to group I (adjusted P = 0.001, adjusted HR = 0.31, 95% CI = 0.16-0.61 and adjusted P = 0.043, adjusted HR = 0.63, 95%CI = 0.41-0.99, respectively). NOD2 and NLRX1 expression levels are potential prognostic markers in HCC following hepatectomy.
| S-EPMC5673949 | biostudies-literature
Project description:Aims: A large number of studies have suggested that exportins (XPOs) play a pivotal role in human cancers. In the present study, we analyzed XPO mRNA expression in cancer tissues and explored their prognostic value in hepatocellular carcinoma (HCC).Methods: Transcriptional and survival data related to XPO expression in HCC patients were obtained through the ONCOMINE and UALCAN databases. Survival analysis plots were drawn with Gene Expression Profiling Interactive Analysis (GEPIA). Sequence alteration data for XPOs were obtained from The Cancer Genome Atlas (TCGA) database and c-BioPortal. Gene functional enrichment analyses were performed with Database for Annotation, Visualization and Integrated Discovery (DAVID).Results: Compared with normal liver tissues, significant XPO mRNA overexpression was observed in HCC cancer tissues. There was a trend of higher XPO expression in more advanced clinical stages and lower differentiated pathological grades of HCC. In HCC patients, high expression of XPO1, CSE1L, XPOT, XPO4/5/6 was related to poor overall survival (OS), and XPO1, CSE1L and XPO5/6 were correlated with poor disease-free survival (DFS). The main genetic alterations in XPOs involved mRNA up-regulation, DNA amplification and deletion. General XPO mutations were remarkably associated with worse OS and mostly affected the pathways of RNA transport and oocyte meiosis.Conclusion: High expression of XPOs was associated with a poor prognosis in HCC patients. XPOs may be exploited as good prognostic biomarkers for survival in HCC patients.
| S-EPMC6702357 | biostudies-literature
Project description:The BolA gene family member (BOLA1-3) plays an important role in regulating normal and pathological biological processes including liver tumorigenesis. However, their expression patterns as prognostic factors in hepatocellular carcinoma (HCC) patients have not to be elucidated. We examined the transcriptional expressions and survival data of BolA family member in patients with HCC from online databases including ONCOMINE, TCGA, UALCAN, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, SurvExpress, cBioPortal, and Exobase. Network molecular interaction views of BolA family members and their neighborhoods were constructed by the IntAct web server. In our research, we had found that the expression levels of BolA /2/3 mRNA were higher in HCC tissue than in normal liver tissues from TGCA databases. Moreover, the BolA family gene expression level is significantly associated with distinct tumor pathological grade, TMN stage, and overall survival (OS). The BolA family can be considered as prognostic risk biomarkers of HCC. A small number of BolA gene-mutated samples were detected in the HCC tissue. IntAct analysis revealed that BolA1/2/3 was closely associated with the GLRX3 expression in HCC, which is implicated in the regulation of the cellular iron homeostasis and tumor growth. Furthermore, prognostic values of altered BolAs and their neighbor GLRX3 gene in HCC patients were validated by SurvExpress analysis. In conclusion, the membrane BolA family identified in this study provides very useful information for the mechanism of hepatic tumorigenesis.
| S-EPMC9398796 | biostudies-literature
Project description:The aim of the present study was to investigate the diagnostic and prognostic value of Wingless‑type MMTV integration site (WNT) gene family expression in patients with hepatitis B virus (HBV)‑related hepatocellular carcinoma (HCC). The clinical data of the patients and gene expression levels were downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Receiver operating characteristic curve analysis was used to investigate the diagnostic value of WNT genes. Cox proportional hazard regression analysis and Kaplan‑Meier survival analysis were performed to evaluate the association of WNT gene expression level with overall survival (OS) and recurrence‑free survival (RFS). A nomogram was constructed for the prediction of prognosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Diagnostic receiver operating characteristic curve analysis suggested that WNT2 had a high diagnostic value, with an area under the curve (AUC) of >0.800 (P<0.0001, AUC=0.810, 95% CI: 0.767‑0.852). Survival analysis indicated that the expression level of WNT1 was significantly associated with OS and RFS (adjusted P=0.033, adjusted HR=0.607, 95% CI: 0.384‑0.960; and adjusted P=0.007, adjusted HR=0.592, 95% CI: 0.404‑0.868, respectively). In the TCGA validation cohort, we also observed that WNT2 was significantly differentially expressed between HCC tissues and adjacent non‑tumor tissues, and WNT1 was associated with both the OS and RFS of HCC. Therefore, through the GSE14520 HBV‑related HCC cohort we concluded that WNT2 may serve as a diagnostic biomarker and WNT1 may serve as a prognostic biomarker. These results may also be extended to TCGA HCC verification cohort.
| S-EPMC6667889 | biostudies-literature
Project description:BackgroundThe members of the cell division cycle-associated (CDCA) gene family are significant regulators of cell proliferation known to play key roles in various cancers. However, the function of CDCA genes in hepatocellular carcinoma (HCC) is unclear. The aim of this research was to clarify the roles of CDCA family members in HCC using bioinformatics analysis tools.MethodsWe studied data on the mRNA and protein expression of CDCA genes and survival in patients with HCC using the Oncomine, UALCAN, HPA, CCLE, LinkedOmics, cBioPortal, and Metascape databases.ResultsSignificant overexpression of all CDCA members was found in HCC tissues. The expression levels of CDCAs were related to the tumor stage, and high expression levels were correlated with a low survival rate in patients with HCC. Also, we observed a high mutation rate (45%) of CDCAs in the HCC samples, which manifested as deep deletion, amplification, or increased mRNA expression. In the correlation analysis, we found that any 2 CDCA members were significantly positively correlated with each other. Cycle-related genes including AHCTF1, AKT1, BIRC5, CENPF, CENPL, and CENPQ were closely associated with CDCA gene alterations.ConclusionsThe findings of this study indicate that CDCAs may be potential therapeutic targets and prognostic indicators for patients with HCC.
| S-EPMC8107601 | biostudies-literature
Project description:PurposeGamma-glutamyl transpeptidase (GGT) family genes play crucial roles in the formation and progression of several solid tumors. However, the expression patterns and the prognostic significance of GGT members in hepatocellular carcinoma (HCC) remain unknown. This study was designed to determine the expression profiles of GGT family members in HCC and validate the prognostic value of serum GGT protein in patients with HCC.MethodWe comprehensively searched public resources based on the LIHC dataset to determine the expression patterns, prognostic significance, DNA methylation status, immune infiltration, and biological pathways of GGT family genes in HCC. Subsequently, we validated the prognostic value of serum GGT protein in 85 patients with early-stage HCC subjected to curative hepatectomy from the Renmin Hospital of Wuhan University.ResultsExcept for GGT1, other GGT family members (GGT5, GGT6, and GGT7) were found to be differentially expressed in primary HCC samples (N = 371) and normal control tissues (N = 50). Furthermore, a positive relationship was not only observed between GGT1 and GGT5 (Spearman coefficient: 0.24, P = 5.143 × 10-6) but also between GGT5 and GGT6 (Spearman coefficient: 0.38, P = 1.24 × 10-13). The expression of GGT1, GGT5, and GGT7 was correlated with overall survival (OS), and GGT7 was associated with disease-free survival (DFS) in patients with HCC. Negative associations between DNA methylation and expression of mRNA were observed for GGT1 (Spearman coefficient: -0.38, P = 6.24e-14), GGT6 (Spearman coefficient: -0.29, P = 1.23e-8), and GGT7 (Spearman coefficient: -0.34, P=6.7e-11). GGT family genes were well correlated with the infiltration levels of immune cells in HCC, especially CD4+ T cells, macrophages, and dendritic cells. Finally, when validated with clinical data from the Renmin cohort, a high expression of serum GGT protein was identified as a strong prognostic element of unfavorable OS (HR = 3.114, P = 0.025), but not of DFS (HR = 1.198, P = 0.05) in patients with HCC subjected to curative hepatectomy.ConclusionTo our knowledge, this is the first comprehensive analysis of the expression patterns and clinical value of GGT family genes in patients with HCC. Our study laid the foundation for the clinical application of the GGT protein in the survival assessment of patients with HCC.
| S-EPMC8426663 | biostudies-literature
Project description:Metabolic changes are the markers of cancer and have attracted wide attention in recent years. One of the main metabolic features of tumor cells is the high level of glycolysis, even if there is oxygen. The transformation and preference of metabolic pathways is usually regulated by specific gene expression. The aim of this study is to develop a glycolysis-related risk signature as a biomarker via four common cancer types. Only hepatocellular carcinoma was shown the strong relationship with glycolysis. The mRNA sequencing and chip data of hepatocellular carcinoma, breast invasive carcinoma, renal clear cell carcinoma, colorectal adenocarcinoma were included in the study. Gene set enrichment analysis was performed, profiling three glycolysis-related gene sets, it revealed genes associated with the biological process. Univariate and multivariate Cox proportional regression models were used to screen out prognostic-related gene signature. We identified six mRNAs (DPYSL4, HOMER1, ABCB6, CENPA, CDK1, STMN1) significantly associated with overall survival in the Cox proportional regression model for hepatocellular carcinoma. Based on this gene signature, we were able to divide patients into high-risk and low-risk subgroups. Multivariate Cox regression analysis showed that prognostic power of this six gene signature is independent of clinical variables. Further, we validated this data in our own 55 paired hepatocellular carcinoma and adjacent tissues. The results showed that these proteins were highly expressed in hepatocellular carcinoma tissues compared with adjacent tissue. The survival time of high-risk group was significantly shorter than that of low-risk group, indicating that high-risk group had poor prognosis. We calculated the correlation coefficients between six proteins and found that these six proteins were independent of each other. In conclusions, we developed a glycolysis-related gene signature that could predict survival in hepatocellular carcinoma patients. Our findings provide novel insight to the mechanisms of glycolysis and it is useful for identifying patients with hepatocellular carcinoma with poor prognoses.
| S-EPMC6932884 | biostudies-literature
Project description:Cell division cycle associated (CDCA) gene family plays an important role in cells. However, some researchers revealed that overexpression of CDCAs might contribute to the tumor progression in several cancers. Here, we analyzed the role of this gene family in hepatocellular carcinoma (HCC). We used several web tools and found that most of CDCAs were highly expressed in tumor tissues compared to the paracancer tissues in HCC. We then used RT-qPCR to confirm our results. The results showed that CDCA2, CDCA3, CDCA5 and CDCA8 were up-regulated in HCC. We also found that these genes were associated with poor overall survival and relapse free survival except CDCA7. The functional analysis showed that this gene family might take part in many processes, including cell division, apoptosis, DNA damage and DNA repair, which might contribute to the tumor progression. The KEGG pathway analysis showed that these genes participated in several important pathways such as PI3K-Akt signaling pathway and hippo signaling pathway. In conclusion, our findings suggested that CDCA2, CDCA3, CDCA4, CDCA5, and CDCA8 might have potential diagnostic and prognostic values for hepatocellular carcinoma.
| S-EPMC7477449 | biostudies-literature