目的:构建基于免疫相关基因的宫颈癌预后模型,寻找宫颈癌预后相关的分子标志物.方法:利用TCGA数据库中宫颈癌的转录组信息及临床数据,运用生物信息学方法分析在宫颈癌中差异表达的免疫相关基因,筛选出与患者生存相关的免疫基因,KEGG进行富集分析.逐步回归分析构建可作为预后评估的风险评分模型并评价其预测能力.通过Cox回归进行独立预后分析,同时鉴定出与临床参数相关的免疫预后基因,分析它们与肿瘤微环境中免疫细胞浸润的相关性.结果:在宫颈癌及正常组织中共筛选出5565 个差异表达基因,其中免疫相关基因 339 个,Cox分析显示有 24 个基因与患者预后相关,经逐步回归分析最终确定 12 个免疫相关基因(TNF、TFRC、APOBEC3H、CSK、OLR1、PTPN6、SBDS、AGT、TGFA、IL17RD、NRP1、ZAP70)并构建风险评分模型.生存分析显示,高风险组患者的总生存期明显低于低风险组(P<0.01).ROC曲线下面积为0.75.患者的风险评分与临床分期密切相关(P<0.01),但与年龄、肿瘤分级无相关性(P>0.05).相关性分析筛选出2 个与预后显著相关的免疫基因(OLR1 和ZAP70).OLR1 和ZAP70 基因表达量与肿瘤微环境中的CD8+T细胞、CD4+T细胞、NKT细胞、树突状细胞、辅助性T细胞等具有高度正相关.结论:宫颈癌中有多个免疫相关基因异常表达,且与患者预后紧密相关,基于免疫基因构建的风险评分模型可有效预测患者预后,为宫颈癌的免疫治疗提供潜在的治疗靶点.
Objective:To construct a prognostic model of cervical cancer based on im-munogenomics and to search for tumor prognostic molecules of cervical cancer(CC).Methods:Based on the transcriptome and clinical data of CC from TCGA database,differential immune-related genomes which closely related to the prognosis were analyzed by bioinformatics meth-ods.KEGG enrichment analysis was used to analyze the pathways and functions enriched by prognostic-related immune genes.Cox regression was used to construct a riskscore model to pre-dict the prognosis of patients and then its clinical value was evaluated.Then,independent prog-nostic analysis was used to identify immune prognostic genes associated with clinical character-istics,and to analyze their correlation with immune cell infiltration in tumor microenvironment.Results:5565 genes were differentially expressed in CC tissues and normal tissues,among which 339 were immune-related genes.Univariate Cox analysis showed that 24 immune genes were associated with prognosis.12 key prognostic genes(TNF,TFRC,APOBEC3H,CSK,OLR1,PTPN6,SBDS,AGT,TGFA,IL17RD,NRP1,ZAP70)finally determined via stepwise re-gression analysis to construct the riskscore model.K-M survival analysis showed that the overall survival of patients in the high-risk group was significantly lower than that of the low-risk group(P<0.01).The area under ROC curve was 0.75.In addition,the riskscore could reflect the clinical stage of patients(P<0.01),but there was no correlation with the age,and differentia-tion of tumor(P>0.05).Finally,two immune genes(OLR1 and ZAP70)were screened by cor-relation analysis.Moreover,the expression levels of OLR1 and ZAP70 were positively correlated with CD8+T cells,CD4+T cells,NKT cells,dendritic cells and helper T cells in tumor microen-vironment.Conclusion:Many immune-related genes in CC have abnormal expression,which are closely related to the prognosis of patients.The riskscore model based on it can effectively pre-dict the prognosis of patients and provide two new potential therapeutic target for immunothera-py of CC.
林丽娜;何中慧;陈军莹
广西医科大学第一附属医院妇产科,南宁 530021
临床医学
宫颈癌;免疫基因;预后模型;预后标志物
Cervical cancer;Immune gene;Prognosis model;Prognostic markers
《现代妇产科进展》 2024 (006)
417-426 / 10
国家自然科学基金资助项目(No:81860457);中国博士后科学基金面上项目(No:2019M663411);广西重点研发项目(No:桂科AB23026003);广西医疗卫生适宜技术开发与推广应用项目(No:S2022073)
10.13283/j.cnki.xdfckjz.2024.06.034
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