Identification of prognostic biomarkers for hepatocellular carcinoma based on the m6A RNA modification

The objective of this study was to identify the prognostic biomarkers for hepatocellular carcinoma (HCC) by analyzing the N6-methyladenosine (m6A) RNA modification. HCC is a complex malignant tumor induced by various pathogenic factors. m6A RNA modification and its regulators influence the tumorigenesis and advancement of HCC. RNA sequencing and clinical data were extracted from the TCGA-LIHC and ICGC-LIRI-JP database. Single-cell RNA sequencing data were processed using Seurat and Harmony packages. ConsensusClusterPlus identified molecular subtypes, and ssGSEA quantified m6A regulator-related gene sets. Differentially expressed genes were analyzed, followed by the establishment of a risk model. qRT-PCR validated mRNA expression in Huh7, Hep 3B, and Hep G2 cells and normal hepatocytes. Four molecular subtypes based on m6A regulator transcriptional profiles of m6A regulators were identified, each exhibiting unique clinical, prognostic, and pathway characteristics. A robust risk model distinguished the high- and low-risk groups, revealing obvious differences in immune cells infiltration and chemotherapeutic drug sensitivity. qRT-PCR confirmed significant differential expression of key genes (TRNP1, KIF20A, and CFRHR3) in HCC cell lines and normal hepatocytes. In conclusion, the established risk model may serve as a perspective tool for prognostic prediction, and provide insights into the functions of m6A involved in HCC.