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Integrated Multi-Omics Analysis Uncovers Immune–Metabolic Interplay in Hepatocellular Carcinoma Tumor Microenvironment.

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Title: Integrated Multi-Omics Analysis Uncovers Immune–Metabolic Interplay in Hepatocellular Carcinoma Tumor Microenvironment.
Authors: Park, Jong-Heon, Sim, Dae Won, Kim, Sook-Young, Choi, Joon Young, Hyun, Seung Hyup, Joung, Je-Gun
Source: Cancers; Nov2025, Vol. 17 Issue 21, p3565, 16p
Subject Terms: RESEARCH funding, DNA methylation, BIOINFORMATICS, KAPLAN-Meier estimator, LOG-rank test, COMPARATIVE studies, SURVIVAL analysis (Biometry), GENETIC mutation, HEPATOCELLULAR carcinoma, SEQUENCE analysis
Geographic Terms: SOUTH Korea
Abstract: Simple Summary: This study addresses the urgent need to better understand hepatocellular carcinoma (HCC), a highly lethal cancer, by analyzing the tumor microenvironment (TME). Using multiple omics profiling of HCC patients, we classified tumors by immune activity and discovered significant metabolic and immune-related genes (AGXT2, DPYS, and TNFSF8) whose expression is epigenetically regulated. Single-cell RNA sequencing revealed the cell type-specific roles of these genes, which link higher expression with improved prognosis. By elucidating the intersection of metabolic, immune, and epigenetic regulation, this study offers insights to propose new therapeutic targets and advance precise therapeutic strategies in HCC. Background: Hepatocellular carcinoma (HCC) is one of the most common malignant liver tumors worldwide and is associated with a high mortality rate. Methods: In this study, we performed an integrated multi-omics analysis to characterize the immune and metabolic features of the tumor microenvironment (TME) in HCC. Tumor samples from 60 HCC patients were stratified into two groups based on immune activity score, and differentially expressed genes as well as differentially methylated regions were identified between these groups. Results: Our analysis identified key markers including AGXT2 and DPYS (metabolism-related genes) and TNFSF8 (an immune-related gene). Their increased expression, driven by promoter hypomethylation, was linked to distinct TME profiles. Furthermore, single-cell RNA sequencing revealed cell type-specific expression patterns of these genes, and their higher expression levels were correlated with favorable patient prognosis. Conclusions: These findings demonstrate that the interplay between metabolic pathways and epigenetic regulation of immune genes strongly influences the HCC microenvironment and clinical outcomes. The identified genes could serve as promising therapeutic targets, emphasizing the importance of multi-omics approaches in dissecting tumor heterogeneity. [ABSTRACT FROM AUTHOR]
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Database: Complementary Index
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Abstract:Simple Summary: This study addresses the urgent need to better understand hepatocellular carcinoma (HCC), a highly lethal cancer, by analyzing the tumor microenvironment (TME). Using multiple omics profiling of HCC patients, we classified tumors by immune activity and discovered significant metabolic and immune-related genes (AGXT2, DPYS, and TNFSF8) whose expression is epigenetically regulated. Single-cell RNA sequencing revealed the cell type-specific roles of these genes, which link higher expression with improved prognosis. By elucidating the intersection of metabolic, immune, and epigenetic regulation, this study offers insights to propose new therapeutic targets and advance precise therapeutic strategies in HCC. Background: Hepatocellular carcinoma (HCC) is one of the most common malignant liver tumors worldwide and is associated with a high mortality rate. Methods: In this study, we performed an integrated multi-omics analysis to characterize the immune and metabolic features of the tumor microenvironment (TME) in HCC. Tumor samples from 60 HCC patients were stratified into two groups based on immune activity score, and differentially expressed genes as well as differentially methylated regions were identified between these groups. Results: Our analysis identified key markers including AGXT2 and DPYS (metabolism-related genes) and TNFSF8 (an immune-related gene). Their increased expression, driven by promoter hypomethylation, was linked to distinct TME profiles. Furthermore, single-cell RNA sequencing revealed cell type-specific expression patterns of these genes, and their higher expression levels were correlated with favorable patient prognosis. Conclusions: These findings demonstrate that the interplay between metabolic pathways and epigenetic regulation of immune genes strongly influences the HCC microenvironment and clinical outcomes. The identified genes could serve as promising therapeutic targets, emphasizing the importance of multi-omics approaches in dissecting tumor heterogeneity. [ABSTRACT FROM AUTHOR]
ISSN:20726694
DOI:10.3390/cancers17213565