A novel DNA methylation-driver gene signature for long-term survival prediction of hepatitis-positive hepatocellular carcinoma patients

Abstract

Background: Abnormal DNA methylation is one of the most general epigenetic modifications in hepatocellular carcinoma (HCC). Recent research showed that DNA methylation was a prognostic indicator of all-cause HCC and nonviral HCC. However, whether DNA methylation-driver genes could be used for predicting survival, the probability of hepatitis-positive HCC remains unclear.

Methods: In this study, DNA methylation-driver genes (MDGs) were screened by a joint analysis of methylome and transcriptome data of 142 hepatitis-positive HCC patients. Subsequently, a prognostic risk score and nomogram were constructed. Finally, correlation analyses between the risk score and signaling pathways and immunity were conducted by GSVA and CIBERSORT.

Results: Through random forest screening and Cox progression analysis, 10 prognostic methylation-driver genes (AC008271.1, C11orf53, CASP8, F2RL2, GBP5, LUCAT1, RP11-114B7.6, RP11-149I23.3, RP11-383 J24.1, and SLC35G2) were screened out. As a result, a prognostic risk score signature was constructed. The independent value of the risk score for prognosis prediction were addressed in the TCGA-HCC and the China-HCC cohorts. Next, clinicopathological features were analyzed and HBV status and histological grade were screened to construct a nomogram together with the risk score. The prognostic efficiency of the nomogram was validated by the calibration curves and the concordance index (C index: 0.829, 95% confidence interval: 0.794-0.864), while its clinical application ability was confirmed by decision curve analysis (DCA). At last, the relationship between the risk score and signaling pathways, as well as the correlations between immune cells were elucidated preliminary.

Conclusions: Taken together, our study explored a novel DNA methylation-driver gene risk score signature and an efficient nomogram for long-term survival prediction of hepatitis-positive HCC patients.

Keywords: DNA methylation-driver gene; hepatitis-positive HCC; nomogram; prognosis; risk score.