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SNP rs2057482 in HIF1A gene predicts clinical outcome of aggressive hepatocellular carcinoma patients after surgery.

ABSTRACT: Hypoxia-inducible factor 1? (HIF-1?) plays an important role in tumor growth and metastasis. Genetic variations of HIF1A gene have been shown to influence the developing risk and prognosis in many types of human malignancies. However, their association with clinical outcomes of hepatocellular carcinoma (HCC) patients remains unclear. To investigate the predictive role of single nucleotide polymorphisms (SNPs) in HIF1A gene in HCC patients' outcomes, we genotyped three functional SNPs (rs2057482, rs1957757 and rs2301113) in HIF1A gene and assessed their associations with clinicopathological parameters and prognosis of 492 surgical HCC patients. The patients with variant alleles (CT+TT) of SNP rs2057482 had a significantly lower recurrence risk when compared with patients with the CC genotype. In stratified analysis, the protective effect of rs2057482 CT+TT genotype was more evident in patients with adverse strata, compared with patients with favorable strata. Additionally, strong joint predictive effect between rs2057482 genotypes and AFP level, stage or differentiation were observed. Functional assay also indicated the significant effect of rs2057482 on gene expression. In conclusion, SNP rs2057482 in HIF1A gene is significantly associated with clinical outcomes of Chinese HCC patients after surgery, especially in those with aggressive status, which warrants further validation in other patient populations.

SUBMITTER: Guo X

PROVIDER: S-EPMC4481773 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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SNP rs2057482 in HIF1A gene predicts clinical outcome of aggressive hepatocellular carcinoma patients after surgery.

Guo Xu X Li Deyang D Chen Yibing Y An Jiaze J Wang Kan K Xu Zhuding Z Chen Zhinan Z Xing Jinliang J

Scientific reports 20150626

Hypoxia-inducible factor 1α (HIF-1α) plays an important role in tumor growth and metastasis. Genetic variations of HIF1A gene have been shown to influence the developing risk and prognosis in many types of human malignancies. However, their association with clinical outcomes of hepatocellular carcinoma (HCC) patients remains unclear. To investigate the predictive role of single nucleotide polymorphisms (SNPs) in HIF1A gene in HCC patients' outcomes, we genotyped three functional SNPs (rs2057482, ...[more]

PMID: 26115041

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Project description:BackgroundCumulative evidences have been implicated cancer stem cells in the tumor environment of hepatocellular carcinoma (HCC) cells, whereas the biological functions and prognostic significance of stemness related genes (SRGs) in HCC is still unclear.MethodsMolecular subtypes were identified by cumulative distribution function (CDF) clustering on 207 prognostic SRGs. The overall survival (OS) predictive gene signature was developed, internally and externally validated based on HCC datasets including The Cancer Genome Atlas (TCGA), GEO and ICGC datasets. Hub genes were identified in molecular subtypes by protein-protein interaction (PPI) network analysis, and then enrolled for determination of prognostic genes. Univariate, LASSO and multivariate Cox regression analyses were performed to assess prognostic genes and construct the prognostic gene signature. Time-dependent receiver operating characteristic (ROC) curve, Kaplan-Meier curve and nomogram were used to assess the performance of the gene signature.ResultsWe identified four molecular subtypes, among which the C2 subtype showed the highest SRGs expression levels and proportions of immune cells, whereas the worst OS; the C1 subtype showed the lowest SRGs expression levels and was associated with most favorable OS. Next, we identified 11 prognostic genes (CDX2, PON1, ADH4, RBP2, LCAT, GAL, LPA, CYP19A1, GAST, SST and UGT1A8) and then constructed a prognostic 11-gene module and validated its robustness in all three datasets. Moreover, by univariate and multivariate Cox regression, we confirmed the independent prognostic ability of the 11-gene module for patients with HCC. In addition, calibration analysis plots indicated the excellent predictive performance of the prognostic nomogram constructed based on the 11-gene signature.ConclusionsFindings in the present study shed new light on the role of stemness related genes within HCC, and the established 11-SRG signature can be utilized as a novel prognostic marker for survival prognostication in patients with HCC.

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SNP rs2057482 in HIF1A gene predicts clinical outcome of aggressive hepatocellular carcinoma patients after surgery.

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SNP rs2057482 in HIF1A gene predicts clinical outcome of aggressive hepatocellular carcinoma patients after surgery.

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