宫颈癌预后相关铁死亡基因的筛选及其预后模型的构建  

Screening of ferroptosis genes related to the prognosis of cervical cancer and construction of a prognostic model

作　　者：陈悦 陈雯昕 蒋溢 张冬[2] 许波群 CHEN Yue;CHEN Wenxin;JIANG Yi;ZHANG Dong;XU Boqun(Department of Obstetrics and Gynecology,Sir Run Run Hospital,Nanjing Medical University,Nanjing 211112,Jiangsu,China;Department of Obstetrics and Gynecology,the Second Affiliated Hospital of Nanjing Medical University,Nanjing 210003,Jiangsu,China)

机构地区：[1]南京医科大学附属逸夫医院妇产科,南京211112 [2]南京医科大学第二附属医院妇产科,南京210003

出　　处：《中国临床医学》2025年第2期259-267,共9页Chinese Journal of Clinical Medicine

基　　金：江苏省卫生健康委员会2023年度医学科研项目(H2023113);南京市卫生科技发展专项资金项目(YKK21260)。

摘　　要：目的筛选与宫颈癌预后相关的铁死亡基因并构建预后模型。方法从FerrDb数据库获取铁死亡基因,从全基因组关联研究和肿瘤基因图谱数据库获取宫颈癌相关数据,进行全转录组关联研究、共定位分析和差异表达分析,筛选出与铁死亡相关的候选基因,并对基因进行基因本体功能富集分析和京都基因与基因组百科全书通路富集分析。采用单因素Cox回归分析进一步筛选出与宫颈癌预后相关的基因;Kaplan-Meier法分析基因与患者总生存期的关系;通过TIMER数据库分析基因在泛癌中的表达水平。构建2个预后预测模型,模型1纳入年龄和肿瘤分期,模型2纳入年龄、肿瘤分期和预后相关基因,并比较2个模型的预测能力。结果共获取91个与铁死亡相关的候选基因。单因素Cox回归分析显示15个基因与宫颈癌预后相关,CA9、SCD、TFRC、QSOX1和CDO1是影响宫颈癌患者预后的危险因素(P<0.05),PTPN6、ALOXE3、HELLS、IFNG、MIOX、ALOX12B、DUOX1、ALOX15、AQP3和IDO1是保护因素(P<0.05)。15个基因的mRNA表达水平在至少7种癌症中表现出显著上升或下降,TFRC关联的癌症种类最多,为19种。Kaplan-Meier分析显示HELLS、DUOX1和ALOXE3与宫颈癌不良预后有关。模型1预测宫颈癌患者1年和3年总生存率的AUC分别为0.455和0.478,模型2的AUC分别为0.854和0.595,模型2(C-index=0.727)的预测能力优于模型1(C-index=0.502)。结论基于生物信息学筛选出的15个预后相关基因组成的预后模型对宫颈癌患者的生存结局有较好的预测性能,为宫颈癌患者的预后评估提供重要参考价值。Objective To screen ferroptosis genes related to the prognosis of cervical cancer and to construct a prognosis model.Methods Ferroptosis genes were obtained from FerrDb database,and cervical cancer related data were obtained from The Genome-Wide Association Study Catalog database and The Cancer Genome Atlas database.Transcriptome-Wide Association Study,colocalization analysis and differential expression analysis were conducted to screen out candidate ferroptosis genes;Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted on candidate genes.Univariate Cox regression analysis was used to further screen out genes related to the prognosis of cervical cancer.Kaplan-Meier method was used to analyze the relationship between genes and the overall survival of patients.The expression levels of genes in pan-cancer were analyzed through the TIMER database.Two prognostic models were conducted,Model 1 included age and tumor stage,while Model 2 incorporated age,tumor stage,and prognostic genes.The predictive capabilities of the two models were compared.Results A total of 91 candidate genes related to ferroptosis were obtained.Univariate Cox regression analysis showed that 15 genes were associated with the prognosis of cervical cancer.CA9,SCD,TFRC,QSOX1 and CDO1 were risk factors affecting the prognosis of cervical cancer patients(P<0.05),while PTPN6,ALOXE3,HELLS,IFNG,MIOX,ALOX12B,DUOX1,ALOX15,AQP3 and IDO1 were protective factors(P<0.05).The mRNA expression levels of the 15 genes showed significant upregulation or downregulation in at least 7 types of cancers,among which TFRC was associated with the largest number of cancer types.Kaplan-Meier analysis showed that HELLS,DUOX1 and ALOXE3 were associated with poor prognosis in cervical cancer.The AUC of the model 1 for predicting 1-year and 3-year overall survival rates of cervical cancer patients was 0.455 and 0.478,and the AUC of Model 2 was 0.854 and 0.595.Model 2(C-index=0.727)had better predictive ability than Model 1(

关 键 词：宫颈癌 铁死亡基因 预后模型 

分 类 号：R737.33[医药卫生—肿瘤]