摘要
目的:明确脂质相关巨噬细胞(LAMs)特征基因在肝细胞癌(HCC)预后中的作用,构建基于LAMs特征基因的HCC预后风险模型,筛选潜在生物标志物。方法:联合单细胞RNA测序(scRNA-seq)和批量RNA测序(bulk RNA-seq)技术,分析HCC相关数据集(GSE202642、TCGA-LIHC等)。通过细胞聚类与注释明确LAMs亚群特征,经差异表达分析(DEGs)、Cox回归及LASSO回归筛选LAMs特征基因;利用Meta分析验证基因表达稳定性,结合数据库分析基因与巨噬细胞浸润及肿瘤组织表达的关联。结果:成功明确LAMs在HCC样本中的亚群特征;筛选出14个与HCC预后相关的LAMs特征基因,经Meta分析确定8个在多数据集间稳定表达的差异基因,最终筛选出关键基因HMOX1和SPP1。基于这两个核心基因构建的预后风险模型(RS)可有效关联HCC患者预后;HMOX1在肿瘤组织中表达下调,SPP1表达上调,二者均与巨噬细胞浸润及功能调控相关。结论:LAMs特征基因在HCC预后评估中具有重要价值,HMOX1和SPP1可作为HCC精准预后判断及靶向治疗的新生物标志物,为相关研究提供理论依据。
Objective:To clarify the role of lipid-associated macrophages(LAMs)signature genes in the prognosis of hepatocellular carcinoma(HCC),construct an HCC prognostic risk model based on LAMs signature genes,and screen potential biomarkers.Method:Single-cell RNA sequencing(scRNA-seq)and bulk RNA sequencing(bulk RNA-seq)technologies were combined to analyze HCC-related datasets(GSE202642,TCGA-LIHC,etc.).The characteristics of LAMs subsets in HCC samples were clarified through cell clustering and annotation.LAMs signature genes were screened by differential expression analysis(DEGs),Cox regression and LASSO regression.Meta-analysis was used to verify the stability of gene expression,and database analysis was combined to explore the association between genes and macrophage infiltration as well as tumor tissue expression.Results:The characteristics of LAMs subsets in HCC samples were successfully clarified.A total of 14 LAMs signature genes related to HCC prognosis were screened out.Through Meta-analysis,8 differentially expressed genes stably expressed in multiple datasets were identified,and key genes HMOX1 and SPP1 were finally screened out.The prognostic risk score(RS)model constructed based on these two core genes could effectively correlate with the prognosis of HCC patients.HMOX1 was down-regulated in tumor tissues,while SPP1 was up-regulated,both of which were related to macrophage infiltration and functional regulation.Conclusion:LAMs signature genes have important value in HCC prognosis evaluation.HMOX1 and SPP1 can be used as new biomarkers for precise prognosis judgment and targeted therapy of HCC,providing a theoretical basis for related research.
作者
洪晓绿
陈翠霞
潘小平
HONG Xiaolv;CHEN Cuixia;PAN Xiaoping(Department of Infection Disease,Huadu District People's Hospital of Guangzhou,Huadu Institute of Medicine,Guangzhou 510800,China;Department of Clinical Laboratory,Huadu District People's Hospital of Guangzhou,Huadu Institute of Medicine,Guangzhou 510800,China)
出处
《微循环学杂志》
2025年第3期61-67,72,共8页
Chinese Journal of Microcirculation
基金
广州市花都区医疗卫生一般科研专项项目(23-HDWS-005)。
关键词
脂质相关巨噬细胞
关键基因
预后
肝癌
Lipid-associated macrophages
Key genes
Prognosis
Hepatocellular carcinoma
