机构地区:[1]武汉大学人民医院肿瘤中心,湖北武汉430036 [2]武汉经济技术开发区(汉南区)人民医院科研处,湖北武汉430090
出 处:《中国医药导报》2025年第5期132-140,共9页China Medical Herald
基 金:湖北省大健康产业发展专项项目(2019-916-000-001)。
摘 要:目的探讨双硫死亡相关长链非编码RNAs(DRLs)在子宫内膜癌(UCEC)中的表达特征及其预后价值,建立有效的预后模型,并分析其在肿瘤微环境和药物敏感性中的作用。方法从TCGA数据库中下载541例UCEC患者转录组数据和临床信息,按照1∶1的比例分为训练组(271例)和验证组(270例)。使用共表达分析、Cox回归及LASSO回归分析得到DRLs并构建预后模型;根据风险评分的中位值将训练组分为高、低风险组,绘制Kaplan-Meier生存曲线,主成分分析、列线图及校准曲线进行模型验证;使用基因集富集分析、免疫微环境分析、突变谱分析及药物敏感性预测比较高、低风险组的生物学差异。结果共得到3个DRLs(AC244517.7、EMSLR、PRDX6-AS1)用于构建预后模型。生存分析显示,训练组和验证组中高风险组总生存期短于低风险组(P<0.01)。主成分分析显示,构建模型的3个DRLs区分度较强;列线图预测UCEC患者1、3、5年生存率分别为99.7%、98.5%、97.9%;校准曲线结果显示,C指数为0.702。基因集富集分析显示,高风险组显著富集于细胞周期和DNA修复相关通路,而低风险组富集于细胞代谢和免疫应答相关通路。高风险组的基质分数、免疫分数、综合分数低于低风险组(P<0.05)。高风险组TEN、ARID1A、PIK3CA、TTN等基因的突变频率低于低风险组,而TP53、KMT2D基因的突变频率高于低风险组(P<0.05)。药物敏感性分析显示,高风险组奥沙利铂半数抑制浓度(IC50)值高于低风险组,紫杉醇、卡莫司汀、AZD6738、BI-2536和BMS-345541的IC50值低于低风险组(P<0.01)。结论基于3个DRLs构建的预后模型对UCEC患者的预后评估具有潜在的临床应用价值,有助于评估不同风险UCEC患者的基因差异、免疫浸润情况和抗肿瘤药物敏感性,为实现UCEC的个性化治疗提供依据。Objective To investigate the expression characteristics and prognostic value of disulfidptosis-related long non-coding RNAs(DRLs)in uterine corpus endometrial carcinoma(UCEC),establish an effective prognostic model,and analyze their role in the tumor microenvironment and drug sensitivity.Methods A total of 541 cases of UCEC transcriptome data and clinical information were downloaded from the TCGA database and divided into training group(271 cases)and validation group(270 cases)according to the ratio of 1∶1.Coexpression analysis,Cox regression analysis,and LASSO regression analysis were used to obtain DRLs and construct the prognosis model;the training group was divided into high-and low-risk groups according to the median risk score,Kaplan-Meier survival curve was drawn,and the model was verified by principal component analysis,nomogram,and calibration curve;gene set enrichment analysis,immunomicroenvironment analysis,mutagenesis analysis,and drug sensitivity analysis were used to predict the biological differences of high-and low-risk groups.Results Three DRLs(AC244517.7,EMSLR,and PRDX6-AS1)were identified for the prognostic model.Survival analysis showed that the overall survival of high risk group was shorter than that of low risk group(P<0.01).Principal component analysis showed that the three DRLs of the model were highly distinguishable;1-year,3-year,and 5-year survival rates of UCEC patients were 99.7%,98.5%,and 97.9%,respectively;calibration curve results showed that the C-index was 0.702.Gene set enrichment analysis showed that high-risk group was enriched in cell cycle and DNA repair pathways,while low-risk group was enriched in metabolism and immune response pathways.The matrix score,immune score,and composite score of high-risk group were lower than those of low-risk group(P<0.05).The mutation frequency of TEN,ARID1A,PIK3CA,and TTN genes in high-risk group was lower than that in low-risk group,while the mutation frequency of TP53 and KMT2D genes was higher than that in low-risk group(P<0.05).Drug se
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