title: 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.
authors.affiliation: Department of Infectious and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Shi-Hao
authors.initials: SH
authors.lastname: Xu
authors.affiliation: Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Hai-Qing
authors.initials: HQ
authors.lastname: Wang
authors.affiliation: Department of Infectious and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Yi-Jing
authors.initials: YJ
authors.lastname: Cai
authors.affiliation: Department of Ultrasonography, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ying
authors.affiliation: Department of Infectious and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Infectious and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Yu-Qun
authors.initials: YQ
authors.lastname: Wang
authors.affiliation: Department of Infectious and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Shan-Jie
authors.initials: SJ
authors.lastname: Du
authors.affiliation: Department of Infectious and Liver Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.|Institute of Hepatology, Wenzhou Medical University, Wenzhou, China.
authors.forename: Ke-Qing
authors.initials: KQ
authors.lastname: Shi
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
authors.forename: Meng-Tao
authors.initials: MT
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D015331:Cohort Studies; D019295:Computational Biology; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53