Integrated Multi-Omics Analysis of Tumor Microenvironment and Immune Infiltration in Hepatocellular Carcinoma: Implications for Prognosis and Immunotherapy
Authors: ZHANG Wei, LI Ming, WANG Fang, CHEN Jie, LIU Yang, ZHAO Lei, SUN Hong, ZHOU Peng
Hepatocellular carcinoma (HCC) is a highly heterogeneous malignancy with a complex tumor microenvironment (TME) that profoundly influences disease progression and therapeutic response. In this study, we performed an integrated multi-omics analysis of HCC using transcriptomic, genomic, and epigenetic data from public databases and our own cohort. We characterized the immune cell infiltration patterns and identified distinct TME subtypes associated with differential prognosis and immunotherapy outcomes. Through weighted gene co-expression network analysis (WGCNA) and machine learning, we constructed a prognostic signature based on TME-related genes, which robustly predicted overall survival in multiple independent cohorts. Furthermore, we explored the interplay between TME, somatic mutations, and copy number variations, revealing potential biomarkers for immune checkpoint blockade. Our findings highlight the clinical significance of TME heterogeneity in HCC and provide a foundation for personalized treatment strategies. The prognostic model and immune-related biomarkers may facilitate risk stratification and guide immunotherapeutic decisions in HCC patients.