基于TGF-β相关基因构建并验证子宫内膜癌风险预后模型  

The risk and prognosis model of endometrial cancer was constructed and validated based on TGF-β-related genes

作　　者：申智慧 王志启[1,2] 李赫 李立伟 翟茁钰 王建六 杨潇[1] Shen Zhihui;Wang Zhiqi;Li He(Department of Obstetrics and Gynecology,Peking University People's Hospital,Beijing 100044;Beijing Friendship Hospital,Capital Medical University,Beijing 100050)

机构地区：[1]北京大学人民医院妇产科,北京100044 [2]首都医科大学附属北京友谊医院,北京100050

出　　处：《现代妇产科进展》2024年第6期401-409,共9页Progress in Obstetrics and Gynecology

基　　金：国家自然科学基金资助项目(No:81972426);国家自然科学基金青年项目(No:82203568)。

摘　　要：目的:探索基于TGF-β相关基因的子宫内膜癌(EC)预后模型,用于精准评估EC患者的预后。方法:从TCGA数据库下载EC患者的基因表达谱数据和临床资料。筛选EC和正常组织差异表达的TGF-β相关基因。采用单因素回归分析筛选EC预后相关基因。将TCGA整体人群按1∶1分成训练集和验证集。对训练集人群进行多因素Cox回归分析构建风险预后模型,利用生存分析、ROC曲线等在验证集和整个队列中验证预后模型的预测准确性。分析临床特征与模型之间的相关性,并基于TGF-β相关基因预后模型和独立预后的临床特征因素建立Nomogram图。在体外验证BMPR1B对EC生物学功能的影响。结果:构建并验证了6个TGF-β相关基因(PPP2R1B、GDF7、E2F5、BMPR1B、GDF6、TNF)的EC预后模型。K-M曲线分析提示,高风险评分患者较低风险评分患者预后更差。ROC曲线分析提示,该预后模型对于预测患者1、3、5年生存率具有较好的准确性。GESA富集分析显示,与低风险患者相比,高风险患者在细胞周期、DNA复制等方面作用显著。基于TGF-β相关基因和临床特征因素构建了Nomogram图,校准曲线评估其预测准确性较好。敲低BMPR1B表达可显著抑制EC的增殖、迁移和侵袭。结论:本研究构建并验证了一种基于TGF-β相关基因的EC患者预后模型,该模型可用于准确预测EC患者的预后,并基于独立预后因素构建Nomogram图,有助于协助临床医生准确判断患者预后并做出最佳临床决策。BMPR1B是EC的潜在治疗靶点。Objective:To explore an endometrial cancer(EC)prognostic model based on TGF-β-related genes to accurately evaluate the prognosis of EC patients.Methods:Download the gene expression data and clinical data of EC patients from the TCGA database.We screened TGF-β-related genes that were differentially expressed in EC and normal tissues.Single factor regression analysis was used to screen for genes associated with endometrial cancer prognosis.The whole TCGA population was further divided into training set and verification set according to 1∶1 ratio.Multivariate Cox regression analysis was performed on the training set population to build a risk prognosis model,and survival analysis and ROC curve analysis were used to verify the prediction accuracy of the prognosis model in the validation set and the whole set.We also analyzed the correlation between the clinical features and the model,and established a Nomogram based on the TGF-β-related gene prognostic model and independent prognostic clinical features.In addition,we validated the effect of BMPR1B on EC biological function in vitro.Results:We constructed and validated the EC prognostic model of six TGF-β-related genes(PPP2R1B,GDF7,E2F5,BMPR1B,GDF6,TNF).K-M curve analysis suggested that patients with high risk score had worse prognosis than those with low risk score.ROC curve analysis suggested that this prognostic model had good accuracy in predicting the 1,3,and 5-year survival rate of patients.GESA enrichment analysis showed that high-risk patients had significant improvements in cell cycle and DNA replication compared with low-risk patients.A Nomogram was constructed based on TGF-β-related genes and clinical characteristics,and the calibration curve evaluated its prediction accuracy.Further,we found that knocking down the expression of BMPR1B could significantly inhibit the proliferation,migration,and invasion of EC.Conclusions:In this study,we constructed and validated a TGF-β-related gene prognostic model for EC patients,which can be used to accurately p

关 键 词：子宫内膜癌 TGF-Β 预后模型 风险评分 NOMOGRAM 

分 类 号：R737.33[医药卫生—肿瘤]