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

Authors Li N, Zhao L, Guo C, Liu C, Liu Y

Received 12 February 2019

Accepted for publication 19 July 2019

Published 6 August 2019 Volume 2019:11 Pages 7473—7484


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Yong Teng

Na Li,1 Lan Zhao,2 Chunyan Guo,3 Chang Liu,4 Yongyu Liu4

1Department 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 China

Purpose: 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

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