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 includingAGXT2andDPYS(metabolism-related genes) andTNFSF8(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.
背景:肝细胞癌(HCC)是全球范围内最常见的肝脏恶性肿瘤之一,具有较高的死亡率。 方法:本研究通过整合多组学分析,系统描绘了HCC肿瘤微环境(TME)的免疫与代谢特征。基于免疫活性评分,我们将60例HCC患者的肿瘤样本分为两组,并识别出两组间差异表达基因及差异甲基化区域。 结果:分析发现关键标志物包括代谢相关基因AGXT2和DPYS以及免疫相关基因TNFSF8。这些基因因启动子低甲基化驱动的表达上调与特定的TME特征相关。单细胞RNA测序进一步揭示了这些基因在特定细胞类型中的表达模式,且其高表达水平与患者良好的预后相关。 结论:本研究表明,代谢通路与免疫基因表观遗传调控之间的相互作用显著影响HCC微环境及临床结局。所鉴定的基因有望成为潜在治疗靶点,凸显了多组学方法在解析肿瘤异质性的重要性。