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Prognostic value of DNA repair based stratification of hepatocellular carcinoma.


ABSTRACT: Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p?=?0.004, hazard ratio (HR): 2.989) and tumor-free survival (p?=?0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy.

SUBMITTER: Lin Z 

PROVIDER: S-EPMC4867671 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Prognostic value of DNA repair based stratification of hepatocellular carcinoma.

Lin Zhuo Z   Xu Shi-Hao SH   Wang Hai-Qing HQ   Cai Yi-Jing YJ   Ying Li L   Song Mei M   Wang Yu-Qun YQ   Du Shan-Jie SJ   Shi Ke-Qing KQ   Zhou Meng-Tao MT  

Scientific reports 20160513


Aberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDR  ...[more]

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