基于失巢凋亡相关基因构建膀胱癌预后模型的研究  

Construction of a prognostic model for bladder cancer based on loss-of-nest apoptosis-related genes

作　　者：汪露 陈琳[2,3] 谷延伦 董秉琪 陈洁[2,3] 崔一民 WANG Lu;CHEN Lin;GU Yan-lun;DONG Bing-qi;CHEN Jie;CUI Yi-min(School of Pharmacy,Wenzhou Medical University,Wenzhou 325035,Zhejiang Province,China;Institute of Clinical Pharmacology,Peking University First Hospital,Bejing 100034,China;Department of Pharmacy,Peking University First Hospital,Bejing 100034,China)

机构地区：[1]温州医科大学药学院,浙江温州325035 [2]北京大学第一医院临床药理研究所,北京100034 [3]北京大学第一医院药学部,北京100034

出　　处：《中国临床药理学杂志》2025年第2期240-244,F0003,共6页The Chinese Journal of Clinical Pharmacology

摘　　要：目的在膀胱癌中建立失巢凋亡相关基因(ANRs)预后风险模型,计算风险评分,并分析高、低风险评分的膀胱癌患者与肿瘤微环境的关系。方法通过公共数据库信息和Cox回归分析筛选预后相关的ANRs和临床独立风险因素。用最小绝对值收敛和选择算子算法(LASSO)分析和列线图建立预后风险模型。通过kaplan-meier生存分析和曲线下面积(AUC)验证预后风险模型准确度。通过CIBERSORT(https://cibersortx.stanford.edu/)和单样本基因集富集分析(ssGSEA)探究风险评分与肿瘤微环境的关系。结果预后相关的ANRs分别是B淋巴细胞瘤-2相关启动子(BAD)、细胞周期蛋白依赖性激酶抑制因子3(CDKN3)和增殖细胞核抗原(PCNA),临床独立风险因素分别是性别、年龄、临床分期(T、N)和风险评分。预后风险模型表达为风险评分=(0.1552×BAD表达量)+(0.2286×CDKN3表达量)+(0.0114×PCNA表达量)和列线图。风险评分越低表示膀胱癌患者预后越好,生存曲线1、3、5年的AUC分别为0.732、0.620、0.541,列线图1、3、5年校准曲线几乎为对角对应,体现该模型准确。预后风险模型高、低风险组在膀胱癌肿瘤微环境中免疫细胞浸润方面呈现巨大差异。结论建立的膀胱癌失巢凋亡相关基因预后风险模型准确度高,可以较好地评估膀胱癌患者预后,高、低风险评分的膀胱癌患者与肿瘤微环境关系密切。Objective To develop a prognostic risk model for anoikis-related genes(ANRs)in bladder cancer,calculaterisk scores,and analyze the relationship between bladder cancer patients with high and low risk scores and the tumor microenvironment.Methods Prognosis-related ANRs and clinically independent risk factors were screened by public database information and Cox regression analysis.Prognostic risk modeling was performed by least absolute shrinkage and selection operator(LASSO)analysis and column-line diagrams.Prognostic risk model accuracy was validated by kaplan-meier survival analysis and area under receiver operating characteristic curve(ROC)curve(AUC).The relationship between risk score and tumor microenvironment was explored by CIBERSORT(https://cibersortx.stanford.edu/)and single sample gene set enrichment analysis(ssGSEA).Results The prognostically relevant ANRs were B-lymphoblastoma-2-associated promoter(BAD),cell cycle protein-dependent kinase inhibitor 3(CDKN3),and proliferating cell nuclear antigen(PCNA),and the clinically independent risk factors were gender,age,clinical stage(T,N),and risk score.The prognostic risk model was expressed as risk score=(0.1552×BAD expression)+(0.2286×CDKN3 expression)+(0.0114×PCNA expression)and column line graph.The lower the risk score the better the prognosis of bladder cancer patients,the AUC of the survival curves for 1,3 and 5 years were 0.732,0.620 and 0.541,respectively,and the column line graphs of the 1-,3-and 5-year calibration curves almost corresponded diagonally,reflecting the accuracy of the model.The high and low risk groups of the prognostic risk model showed great differences in immune cell infiltration in the tumor microenvironment of bladder cancer.Conclusion The established prognostic risk model for bladder cancer loss of apoptosis-related genes is highly accurate and can better assess the prognosis of bladder cancer patients,and bladder cancer patients with high and low risk scores are closely related to the tumor microenvironment.

关 键 词：膀胱癌 失巢凋亡 治疗靶点 肿瘤微环境 预后价值 

分 类 号：R979.1[医药卫生—药品]