Hepatitis B-related hepatocellular carcinoma: classification and prognostic model based on programmed cell death genes

Instruction Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Programmed cell death (PCD) is a critical process in suppressing tumor growth, and alterations in PCD-related genes may contribute to the progression of HBV-HCC. This study aims to develop a prognostic model that incorporates genomic and clinical information based on PCD-related genes, providing novel insights into the molecular heterogeneity of HBV-HCC through bioinformatics analysis and experimental validation.Methods In this study, we analyzed 139 HBV-HCC samples from The Cancer Genome Atlas (TCGA) and validated them with 30 samples from the Gene Expression Omnibus (GEO) database. Various bioinformatics tools, including differential expression analysis, gene set variation analysis, and machine learning algorithms were used for comprehensive analysis of RNA sequencing data from HBV-HCC patients. Furthermore, among the PCD-related genes, we ultimately chose DLAT for further research on tissue chips and patient cohorts. Besides, immunohistochemistry, qRT-PCR and Western blot analysis were conducted.Results The cluster analysis identified three distinct subgroups of HBV-HCC patients. Among them, Cluster 2 demonstrated significant activation in DNA replication-related pathways and tumor-related processes. Analysis of copy number variations (CNVs) of PCD-related genes also revealed distinct patterns in the three subgroups, which may be associated with differences in pathway activation and survival outcomes. DLAT in tumor tissues of HBV-HCC patients is upregulated.Discussion Based on the PCD-related genes, we developed a prognostic model that incorporates genomic and clinical information and provided novel insights into the molecular heterogeneity of HBV-HCC. In our study, we emphasized the significance of PCD-related genes, particularly DLAT, which was examined in vitro to explore its potential clinical implications.