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

• Published in: Frontiers in immunology Vol. 15; p. 1411161
• Main Authors: Tian, Jinyue, Meng, Jiao, Yang, Zhenkun, Song, Li, Jiang, Xinyi, Zou, Jian
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 2024
• Subjects: Apoptosis - genetics; Biomarkers, Tumor - genetics; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - virology; clinical characteristics; Computational Biology - methods; DNA Copy Number Variations; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hepatitis B - complications; Hepatitis B - genetics; Hepatitis B - virology; Hepatitis B virus - genetics; hepatitis B virus infection; hepatocellular carcinoma; Humans; Liver Neoplasms - genetics; Liver Neoplasms - virology; Male; Middle Aged; Prognosis; prognostic model; programmed cell death; hepatitis B virus infection; programmed cell death; prognostic model; clinical characteristics; hepatocellular carcinoma
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1411161

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. 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 for further research on tissue chips and patient cohorts. Besides, immunohistochemistry, qRT-PCR and Western blot analysis were conducted. 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. in tumor tissues of HBV-HCC patients is upregulated. 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 , which was examined in vitro to explore its potential clinical implications.