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

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, withp-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.