基于细胞焦亡相关基因表达谱的子宫内膜癌预后模型构建  

Construction of a prognostic model in uterine corpus endometrial carcinoma based on a pyroptosis-related gene signature

作　　者：常晴 刘佳[2] 曲爱林 刘京康[3] Chang Qing;Liu Jia;Qu Ailin(Department of Clinical Laboratory,Qilu Hospital of Shandong University,Jinan 250012;Center for Basic Medical Research,Qilu Hospital of Shandong University,Jinan 250012)

机构地区：[1]山东大学齐鲁医院检验科,济南250012 [2]山东大学齐鲁医院基础医学研究中心,济南250012 [3]山东大学齐鲁医院妇产科,济南250012

出　　处：《现代妇产科进展》2023年第4期248-253,257,共7页Progress in Obstetrics and Gynecology

基　　金：国家自然科学基金资助项目(No:82102481);山东省自然科学基金资助项目(No:ZR2021QH206)。

摘　　要：目的:筛选在子宫内膜癌(UCEC)中具有预后价值的细胞焦亡相关基因并构建风险评分模型,进一步构建整合细胞焦亡基因表达谱和临床病理参数的UCEC预后列线图(Nomogram)。方法:基于癌症基因组图谱数据库(TCGA)筛选UCEC细胞焦亡相关差异表达基因。通过最小绝对收缩和选择算子(Lasso)回归获得细胞焦亡相关预后基因并构建风险评分模型。使用受试者工作特征曲线(ROC)评估模型的特异度和敏感度。根据风险值(risk)的中位数将患者划分为高风险组和低风险组,整合临床病理信息(临床分期、病理分级和肿瘤类型),采用Kaplan-Meier法进行生存分析,使用单样本基因集富集分析(ssGSEA)评估28种免疫细胞浸润丰度。比较高风险组和低风险组的临床病理分型、预后特征和免疫细胞浸润程度的差异。结合临床变量(年龄和临床病理分期),通过逐步回归方法获得最优变量组合建立Nomogram,使用ROC和校准曲线对Nomogram进行评估。结果:13种细胞焦亡基因在UCEC组织中的表达高于癌旁组织(P<0.05)。进一步获得由9种有预后价值的细胞焦亡基因组成的表达谱,并据此构建风险评分模型。预后风险模型1年、3年和5年的生存预测性能AUC值分别是0.627、0.722和0.770。百分比柱状图显示,临床分期、病理分级和肿瘤类型在高风险组、低风险组间所占比例存在差异,高风险组表现出更差的临床分期、病理分级和更高的复发风险。生存分析显示,低风险组患者的总生存期(OS)显著高于高风险组(P<0.001)。ssGSEA分析表明,低风险组中20种免疫细胞的浸润程度高于高风险组(P<0.05)。Nomogram的C指数(C-index)为0.681(95%CI为0.618~0.742,P<0.001),预测总生存时间方面表现出良好的准确性。校准曲线分析显示,校准预测曲线与实际观测结果一致性较高。结论:本研究通过9种细胞焦亡相关基因构建UCEC预后模型,该模型具有良好的预测能Objective:To screen pyroptosis related genes with prognostic value in uterine corpus endometrial carcinoma(UCEC)and construct a risk score model,and the prognostic nomogram of UCEC was further constructed by integrating a pyroptosis-related gene signature and clinical factors.Method:Differentially expressed genes related to pyroptosis were screened based on the Cancer Genome Atlas(TCGA)Database.The prognostic genes related to pyroptosis were obtained by the least absolute contraction and selection operator(Lasso)regression,and the risk score model was then constructed.Receiver operating characteristic(ROC)curve was used to evaluate the specificity and sensitivity of the model.Patients were divided into high-risk group and low-risk group according to the median of risk.Integration of clinicopathological information(clinical stage,pathological grade and tumor type),survival analysis using the Kaplan-Meier method,and assessment of the abundance of 28 immune cell infiltrates using single sample gene set enrichment analysis(ssGSEA).Combined with clinicopathological information,differences in clinicopathological subtypes,prognostic features and degree of immune cell infiltration were compared between high and low risk groups.Clinical variables(age and clinicopathological stage)were combined,and the optimal combination of variables was obtained by stepwise regression method to establish Nomogram.The Nomogram was evaluated using ROC curve and calibration curve analysis.Results:The expression of 13 pyroptosis related genes was higher in UCEC tissues compared with normal tissues adjacent to the cancer(P<0.05).A novel signature based on nine pyroptosis-related prognostic genes was established and a risk score model was constructed.The AUC values of the prognostic risk model at one,three and five years were 0.627,0.722 and 0.770,respectively.The percentage bar chart showed differences in the proportions of clinical stage,pathological grade and tumor type between high and low risk groups.The high-risk group exhibited worse cl

关 键 词：子宫内膜癌 焦亡 TCGA数据库 NOMOGRAM 预后 

分 类 号：R737.33[医药卫生—肿瘤]