Identification of a novel DNA repair-related prognostic signature predicting survival of patients with hepatocellular carcinoma

Na Li,1 Lan Zhao,2 Chunyan Guo,3 Chang Liu,4 Yongyu Liu41Department of Central Laboratory, Shenyang Tenth People’s Hospital, Shenyang Chest Hospital, Shenyang, Liaoning, People’s Republic of China; 2Department of Pharmacology, School of Pharmacy, China Medical University, Shenyan...

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Bibliographic Details
Main Authors: Li N, Zhao L, Guo C, Liu C, Liu Y
Format: Article
Language:English
Published: Dove Medical Press 2019-08-01
Series:Cancer Management and Research
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Online Access:https://www.dovepress.com/identification-of-a-novel-dna-repair-related-prognostic-signature-pred-peer-reviewed-article-CMAR
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Summary:Na Li,1 Lan Zhao,2 Chunyan Guo,3 Chang Liu,4 Yongyu Liu41Department of Central Laboratory, Shenyang Tenth People’s Hospital, Shenyang Chest Hospital, Shenyang, Liaoning, People’s Republic of China; 2Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Department of Pharmacy, Shenyang Tenth People’s Hospital, Shenyang Chest Hospital, Shenyang, Liaoning, People’s Republic of China; 4Department of Thoracic Surgery, Shenyang Tenth People’s Hospital, Shenyang Chest Hospital, Shenyang, Liaoning, People’s Republic of ChinaPurpose: Hepatocellular carcinoma (HCC) is the sixth most lethal neoplasm worldwide. Traditional biomarkers often exploit the relationship between a certain gene and cancer progression, but they cannot predict patient survival or prognosis accurately. We aim to construct a new DNA repair-related gene signature that combines several genes to improve prognosis prediction in HCC.Methods: We selected an HCC mRNA sequencing (mRNA-seq) dataset (n=365) from The Cancer Genome Atlas (TCGA), and gene set enrichment analysis (GSEA) was used to explore bioinformatics information and further screen genes. We then built a gene signature based on the Cox proportional hazards regression model.Results: GSEA revealed that the hallmark DNA repair gene set was significantly upregulated in the tumor phenotype. A set of seven genes, namely, ADA, FEN1, POLR2G, SAC3D1, SEC61A1, SF3A3, and UPF3B, were significantly associated with overall survival (OS) and used to form a gene signature. The signature risk score was calculated and used to divide patients into high‐ and low‐risk groups. The high-risk group showed worse prognosis (log-rank test p<0.0001). Univariate and multivariate Cox regression analysis showed that the prognostic performance of this risk score signature was robust in different subgroups based on clinicopathological features, with p-values <0.05 (HR=2.38, 95% CI (confidence interval) =1.355–4.184), indicating that it can serve as an independent prognostic indicator.Conclusion: We developed and identified a seven‐gene signature related to the DNA repair process that can predict survival in HCC. It can be used as an effective classification tool and to guide clinical treatment.Keywords: DNA repair, hepatocellular carcinoma, mRNAs, prognostic, survival
ISSN:1179-1322