摘要
目的整合单细胞转录组(scRNA-seq)与批量转录组(Bulk RNA-seq)数据,鉴定在肝细胞癌(HCC)恶性克隆及组织水平上均持续失调的核心基因,评估其预后预测价值并探讨其对肿瘤免疫微环境(TIME)的潜在调控作用。方法对scRNA-seq数据进行拷贝数变异(CNV)推断,以识别恶性肝细胞并获取其特异性表达基因。随后,将这些基因与癌症基因组图谱(TCGA)队列中Bulk水平的肿瘤-癌旁差异表达基因取交集,定义为“持续失调基因”。进一步通过蛋白质互作网络(PPI)分析挖掘核心功能模块与枢纽基因,并在独立数据集(GSE14520)和TCGA队列中验证其表达、诊断效能及预后价值。最后利用肿瘤免疫评估资源数据库(TIMER数据库)分析核心基因与免疫细胞浸润的相关性。结果共鉴定出571个持续上调基因。上调基因形成一个由GTPBP4、BOP1、DKC1等组成的核心模块,显著富集于核糖体生物发生(RiBi)和细胞周期通路。该模块基因在验证队列中表现出优异的诊断效能,其高表达与患者总生存期缩短相关(P<0.05)。免疫浸润分析揭示,RiBi核心基因表达与巨噬细胞负相关,而与调节性T细胞及髓源性抑制细胞正相关(P<0.05)。结论RiBi核心基因模块可作为HCC预后预测标志物,其通过双向调控免疫微环境影响HCC进展,提示靶向RiBi通路可能是潜在治疗策略。
Objective To identify core genes persistently dysregulated at both the malignant clone and tissue levels in hepatocellular carcinoma(HCC)based on single-cell RNA sequencing(scRNA-seq)and Bulk RNA sequencing(Bulk RNA-seq),assess their prognostic value,and investigate their potential regulatory role in the tumor immune microenvironment(TIME).Methods Copy number variation(CNV)analysis was performed on the scRNA-seq data to identify malignant hepatocytes and obtain their specifically expressed genes.Subsequently,these genes were intersected with the tumor-versus-adjacent differential expression genes from the bulk RNA-seq data of the cancer genome atlas(TCGA)cohort.The overlapping genes were defined as"persistently dysregulated genes."A protein-protein interaction(PPI)network analysis was further conducted to identify core functional modules and hub genes.Their expression,diagnostic efficacy,and prognostic value were validated in an independent dataset(GSE14520)and the TCGA cohort.Finally,the correlation between the core genes and immune cell infiltration was analyzed using the tumor immune estimation resource(TIMER)database.Results In this study,571 upregulated persistent genes were identified.A core module(e.g.GTPBP4,BOP1,DKC1)emerged from the upregulated genes,enriched in ribosome biogenesis(RiBi)and cell cycle pathways.This module showed high diagnostic accuracy and correlated with shorter overall survival(P<0.05).Immunologically,RiBi core genes were inversely associated with macrophage cell infiltration,but positively with Tregs and MDSCs,indicating a"bidirectional regulation"mode(P<0.05).Conclusions The RiBi core gene module is a prognostic biomarker in HCC,influencing progression through bidirectional immune regulation,suggesting RiBi pathway targeting as a potential therapeutic strategy.
作者
谢文熙
王庆云
李贝棋
叶文彪
张捷
XIE Wenxi;WANG Qingyun;LI Beiqi;YE Wenbiao;ZHANG Jie(Department of Hepatobiliary Surgery,Fuding Hospital,Ningde,Fujian 355200,China;Department of Biliary-Pancreatic Surgery,Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200127,China)
出处
《中国医药指南》
2026年第7期17-20,共4页
Guide of China Medicine
基金
福建省宁德市自然科学基金联合项目(2022J50)。
关键词
肝细胞癌
单细胞转录组
批量转录组
枢纽基因
核糖体生物发生
肿瘤免疫微环境
Hepatocellular carcinoma
Single-cell RNA sequencing
Bulk RNA sequencing
Hub genes
Ribosome biogenesis
Tumor immune microenvironment
