肝细胞癌干性分型及其预后基因GSDMC的研究

Study on stemness typing and prognostic gene GSDMC of hepatocellular carcinoma

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 hepatocellular carcinoma samples from The Cancer Genome Atlas Program databases.The differences in prognosis,tumor microenvironment 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 significant differences in survivalrate,the levels of immune infiltration,and treatment reponse between C1 and C2.Integrating WGCNA,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 characteristics,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.