|国家科技期刊平台
首页|期刊导航|海南医学院学报|肝细胞癌干性分型及其预后基因GSDMC的研究

肝细胞癌干性分型及其预后基因GSDMC的研究OACSTPCD

Study on stemness typing and prognostic gene GSDMC of hepatocellular carcinoma

中文摘要英文摘要

目的:通过肝细胞癌干性分型筛查某些对免疫治疗反应更灵敏的患者,并验证其预后相关基因GSDMC.方法:从StemChecker数据库中提取26个干细胞基因组,采用共识聚类算法对癌症基因组图谱计划数据库中的328个肝细胞癌样本进行干性亚型鉴定.评估两种亚型在预后、肿瘤微环境成分和治疗反应方面的差异.然后,通过加权基因共表达网络分析、Cox回归和随机森林生存分析,筛选预后相关基因.最后,选择预后相关基因GSDMC进行实验验证.结果:根据单样本基因集富集分析,将肝细胞癌患者分为两种亚型(C1和C2).C1和C2在生存率、免疫浸润水平和治疗反应方面存在显著差异.结合WGCNA,Cox回归和随机森林生存分析确定了4个预后相关基因(GSDMC,AOC1,OTX1,CASC9).免疫印迹、免疫组织化学和实时荧光定量PCR表明,GSDMC在肝细胞癌组织和细胞中的表达降低.细胞成球实验表明GSDMC抑制肝细胞癌细胞的干性.结论:鉴定两种不同的干细胞亚型C1和C2,为肝细胞癌的临床异质性及其与预后、TME特征和免疫治疗提供了有价值的见解;GSDMC在肝细胞癌组织和细胞中的表达降低,GSDMC抑制肝细胞癌细胞的干性.

Objective:To screen the patients with hepatocellular carcinoma who are more responsive to immunotherapy by stemness typing,and to verify the prognosis related gene GSDMC.Methods:Twenty-six stem cell genomes were extracted from the StemChecker database,consensus clustering algorithm was applied for the identification of stemness subtypes on 328 hepato-cellular carcinoma samples from The Cancer Genome Atlas Program databases.The differences in prognosis,tumor microenviron-ment components,and treatment response between the two subtypes were assessed.Then,a stem risk model was constructed by integrating weighted gene correlation network analysis,Cox regression and random survival forest analyses.Finally,the prognostic-related gene GSDMC was selected for experimental validation.Results:Based on single-sample gene set enrichment analysis enrichments scores,hepatocellular carcinoma patients were classified into two subtypes(C1 and C2).There were signifi-cant differences in survivalrate,the levels of immune infiltration,and treatment reponse between C1 and C2.Integrating WGC-NA,Cox regression and random forest survival analyses identified four prognostic-related genes(GSDMC,AOC1,OTX1,CASC9).Immunohistochemistry and real-time-quantitative polymerase chain reaction showed that the expression of GSDMC was decreased in hepatocellular carcinoma tissues and cells.Sphere formation assay showed that GSDMC suppressesed hepatocellular carcinoma cells stemness.Conclusion:The identification of two distinct stem cell subtypes,C1 and C2,provides valuable insights into the clinical heterogeneity of hepatocellular carcinoma and its correlation with prognosis,tumor microenvironment characteris-tics,and immunotherapy response rates.The expression of GSDMC is decreased in hepatocellular carcinoma tissues and cells,and GSDMC inhibits the stemness of hepatocellular carcinoma cells.

包凌;龚旋坤;庞青;陈晓

蚌埠医学院第一附属医院老年科,安徽 蚌埠 233000蚌埠医学院第一附属医院肝胆外科,安徽 蚌埠 233000

临床医学

肝细胞癌GSDMC干性肿瘤微环境免疫治疗

Hepatocellular cacinomaGSDMCStemnessTumor microenvironmentImmunotherapy

《海南医学院学报》 2024 (006)

442-450 / 9

This study was supported by Anhui Provincial Natural Science Foundation Project(2008085J37) 安徽省自然科学基金资助项目(2008085J37)

10.13210/j.cnki.jhmu.20231106.001

评论