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Prognostic roles of the transcriptional expression of exportins in hepatocellular carcinoma.

ABSTRACT: 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.

SUBMITTER: Chen L

PROVIDER: S-EPMC6702357 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Prognostic roles of the transcriptional expression of exportins in hepatocellular carcinoma.

Chen Lubiao L Huang Yanlin Y Zhou Liang L Lian Yifan Y Wang Jialiang J Chen Dongmei D Wei Huan H Huang Mingsheng M Huang Yuehua Y

Bioscience reports 20190819 8

<b>Aims:</b> 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).<b>Methods:</b> 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). ...[more]

PMID: 31371628

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Project description:BackgroundThe protein-coding gene RAB22A, a member of the RAS oncogene family, is amplified or overexpressed in certain cancers. However, its action mechanism in hepatocellular carcinoma (HCC) remains unclear. Here, we aimed to examine the connection between RAB22A and survival prognosis in HCC and explore the biological significance of RAB22A.MethodsA database-based pan-cancer expression analysis of RAB22A was performed. Kaplan-Meier analysis and Cox regression were performed to evaluate the association between RAB22A expression and survival prognosis in HCC. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), various potential biological functions and regulatory pathways of RAB22A in HCC were discovered. Tumor immune infiltration was studied using the single sample gene set enrichment analysis (ssGSEA) method. N6-methyladenosine modifications and the regulatory network of competitive endogenous RNA (ceRNA) were verified in the TCGA cohort.ResultsRAB22A was upregulated in HCC samples and cell lines. A high RAB22A expression in HCC was strongly correlated with sex, race, age, weight, TNM stage, pathological stage, tumor status, histologic grade, TP53 mutation status, and alpha fetal protein (AFP) levels. Overexpression of RAB22A indicated a poor prognosis was related to overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). GO and KEGG analyses revealed that the differentially expressed genes related to RAB22A might be involved in the proteasomal protein catabolic process, ncRNA processing, ribosome ribosomal subunit, protein serine/threonine kinase activity, protein serine kinase activity, Endocytosis, and non-alcoholic fatty liver disease. GSEA analyses revealed that the differentially expressed genes related to RAB22A might be involved in the T cell receptor, a co-translational protein, that binds to the membrane, axon guidance, ribosome, phagocytosis, and Eukaryotic translation initiation. RAB22A was correlated with N6-methyladenosine expression in HCC and established RAB22A-related ceRNA regulatory networks. Finally,RAB22A expression was positively connected the levels of infiltrating with T helper cells, Tcm cells, and Th2 cells,In contrast, we observed negatively correlations with cytotoxic cells, DCs, and pDCs cells.Moreover,RAB22A expression showed a strong correlation with various immunomarkergroups in HCC.ConclusionsRAB22A is a potential therapeutic target for improving HCC prognosis and is closely related to immune cell infiltration.

Project description:BackgroundThe copper metabolism MURR1 domain (COMMD) protein family involved in tumor development and progression in several types of human cancer, but little is known about the function of COMMD proteins in hepatocellular carcinoma (HCC).MethodsThe ONCOMINE and the UALCAN databases were used to evaluate the expression of COMMD1-10 in HCC and the association of this family with individual cancer stage and tumor grade. Kaplan-Meier (K-M) Plotter and Cox analysis hint the prognostic value of COMMDs. A network comprising 50 most similar genes and COMMD1-10 was constructed with the STRING database. Gene set enrichment analysis (GSEA) was performed using LinkedOmics database. The correlations between COMMD expression and the presence of immune infiltrating cells were also analyzed by the tumor immune estimation resource (TIMER) database. GSE14520 dataset and 80 HCC patients were used to validated the expression and survival value of COMMD3. Human HCC cell lines were also used for validating the function of COMMD3.ResultsThe expression of all COMMD family members showed higher expression in HCC tissues than that in normal tissues, and is associated with clinical cancer stage and pathological tumor grade. In HCC patients, the transcriptional levels of COMMD1/4 are positively correlated with overall survival (OS), while those of COMMD2/3/7/8/9 are negatively correlated with OS. Multivariate analysis indicated that a high level of COMMD3 mRNA is an independent prognostic factor for shorter OS in HCC patients. However, the subset of patients with grade 3 HCC, K-M survival curves revealed that high COMMD3/5/7/8/9 expression and low COMMD4/10 expression were associated with shorter OS. In addition, the expression of COMMD2/3/10 was associated with tumor-induced immune response activation and immune infiltration in HCC. The expression of COMMD3 from GSE14520 dataset and 80 patients are both higher in tumor than that in normal tissue, and a higher level of COMMD3 mRNA is associated with shorter OS. Knockdown of COMMD3 inhibits human HCC cell lines proliferation in vitro.ConclusionsOur study indicates that COMMD3 is an independent prognostic biomarker for the survival of HCC patients. COMMD3 supports the proliferation of HCC cells and contributes to the poor OS in HCC patients.

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Prognostic roles of the transcriptional expression of exportins in hepatocellular carcinoma.

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Prognostic roles of the transcriptional expression of exportins in hepatocellular carcinoma.

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