A robust panel based on genomic methylation sites for recurrence-free survival in early hepatocellular carcinoma

Abstract

Purpose: Altered gene methylation precedes altered gene expression and the onset of disease. This study aimed to develop a potential model for predicting recurrence of early to mid-stage hepatocellular carcinoma (HCC) using methylation loci. Methods: We used data from early to mid-stage HCC patients (TNM I-II) in the TCGA-LIHC dataset and lasso-cox regression model to identify an 18-DNA methylation site panel from which to calculate the riskScore of patients. The correlation of high/low riskScore with recurrence-free survival (RFS) and immune microenvironment in HCC patients was analyzed by bioinformatics. It was also validated in the GSE56588 dataset and the final dynamic nomogram was constructed. Results: The results showed that riskScore was significantly correlated with RFS in HCC patients. The differential mutated genes between the two groups of HCC patients with high/low riskScore were mainly enriched in the TP53 signaling pathway. The immune microenvironment was better in HCC patients in the low-riskScore group compared to the high-riskScore group. This was validated in the GSE56588 dataset. Based on the subgroup stratification analysis of the relationship between high/low riskScore and RFS, as well as univariate and multivariate cox analyses, the riskScore was found to be independent of clinical indicators. We found that riskScore, vascular invasion and cirrhosis status could effectively differentiate RFS in HCC patients, and we also constructed prediction model based on these three factors. The model we constructed were validated in the TCGA-LIHC database and a web calculator was built for clinical use. Conclusion: The methylation riskScore is a predictor of RFS independent of clinical factors and can be used as a marker to predict recurrence in HCC patients.

Keywords

• Hepatocellular carcinoma
• Methylation riskScore
• Recurrence-free survival
• Immune microenvironment