Diagnostic and prognostic values of the mRNA expression of excision repair cross-complementation enzymes in hepatitis B virus-related hepatocellular carcinoma

Lu Yang,1,* Ming Xu,2,* Chuan-Bao Cui,1 Peng-Hai Wei,1 Shu-Zhi Wu,1 Zuo-Jie Cen,1 Xing-Xing Meng,1 Qiong-Guang Huang,1 Zhi-Chun Xie1 1Department of Epidemiology, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Human Anatomy and Histology and Embryology, Qilu Medical University, Zibo 255213, Shandong Province, People’s Republic of China *These authors contributed equally to this work Background: The current study aims at using the whole genome expression profile chips for systematically investigating the diagnostic and prognostic values of excision repair cross-complementation (ERCC) genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).Materials and methods: Whole genome expression profile chips were obtained from the GSE14520. The receiver-operating characteristic (ROC) curve, survival analysis, and nomogram were used to investigate the diagnostic and prognostic values of ERCC genes. Investigation of the potential function of ERCC8 was carried out by gene set enrichment analysis (GSEA) and genome-wide coexpression analysis.Results: ROC analysis suggests that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated and may have potential to distinguish between HBV-related HCC tumor and paracancerous tissues (area under the curve of ROC ranged from 0.623 to 0.744). Survival analysis demonstrated that high ERCC8 expression was associated with a significantly decreased risk of recurrence (adjusted P=0.021; HR=0.643; 95% CI=0.442–0.937) and death (adjusted P=0.049; HR=0.631; 95% CI=0.399–0.998) in HBV-related HCC. Then, we also developed two nomograms for the HBV-related HCC individualized prognosis predictions. GSEA suggests that the high expression of ERCC8 may have involvement in the energy metabolism biological processes. As the genome-wide coexpression analysis and functional assessment of ERCC8 suggest, those coexpressed genes were significantly enriched in multiple biological processes of DNA damage and repair. Conclusion: The present study indicates that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated between HBV-related HCC tumor and paracancerous tissues and that the mRNA expression of ERCC8 may serve as a potential biomarker for the HBV-related HCC prognosis. Keywords: HBV, hepatocellular carcinoma, diagnosis, prognosis, ERCC