可变剪切联合免疫分析构建膀胱癌预后模型的研究  

Construction of a prognostic model of bladder cancer based on alternative splicing combined with immunoassay

作　　者：王睿昊 成丁财 潘钰 王逢民[1] WANG Ruihao;CHENG Dingcai;PAN Yu;WANG Fengmin(Department of Oncology, Taixing People’s Hospital, Taixing 225400, China)

机构地区：[1]泰兴市人民医院肿瘤科,225400 [2]泰兴市人民医院泌尿外科,225400 [3]泰兴市人民医院病理科,225400

出　　处：《现代泌尿生殖肿瘤杂志》2022年第1期23-30,共8页Journal of Contemporary Urologic and Reproductive Oncology

摘　　要：目的构建基于可变剪切(AS)的膀胱癌预后模型,并探讨其与免疫治疗的关系。方法通过单变量Cox回归分析筛选预后相关AS事件,通过Lasso回归、单变量Cox回归及多元Cox回归构建预后模型并计算风险值(RS)。通过生存分析、受试者工作特征曲线评估模型,并通过列线图可视化模型。利用CIBERSORT、ssGSEA算法进行免疫相关分析。通过差异分析筛选靶基因。结果基于2828例预后相关AS事件,构建了一个包含8个AS事件的预后模型,分析表明RS可以作为膀胱癌的独立预后因素(P<0.05)。RS与CD274等免疫检查点相关基因显著相关,且RS高风险组免疫细胞浸润程度高(P<0.05)。TRMU在肿瘤组织中高表达,TRMU高表达时患者预后较差,PTGER3则相反(P<0.05)。结论基于AS构建的预后模型有助于膀胱癌的临床决策和个性化预后监测。RS相关免疫分析为膀胱癌的发病机制及免疫治疗提供了新的分析方向。TRMU及PTGER3有望成为膀胱癌新的治疗靶点和预后标志物。Objective To establish a prognostic model of bladder cancer(BCa)based on alternative splicing(AS)and to explore its relationship with immunotherapy.Methods Prognostic AS events were screened by univariate Cox regression analysis.Prognostic model was constructed and risk score(RS)was calculated by Lasso regression,univariate Cox regression and multivariate Cox regression.Survival analysis and observer characteristics curve were used to evaluate the model,and through the nomogram the model was visualized.CIBERSORT and ssGSEA algorithms were used for immune analysis.The target genes were screened by variation analysis.Results Based on 2828 cases of prognosis-related AS events,a prognostic model containing eight AS events was constructed.RS can be used as an independent prognostic factor for BCa.There was a significant correlation between RS and other immune checkpoint related genes,such as CD274,and the degree of immune cell infiltration was higher in the high risk group.TRMU is highly expressed in tumor tissues,and patients with high expression of TRMU have a poor prognosis.PTGER3 is on the contrary.Conclusions The prognostic model based on alternative splicing is helpful for clinical decision-making and personalized prognosis monitoring of BCa.RS-related immunoassay provides a new direction for the pathogenesis and immunotherapy of bladder cancer.TRMU and PTGER3 are expected to become new therapeutic targets and prognostic markers for bladder cancer.

关 键 词：可变剪切 免疫微环境 膀胱癌 预后模型 

分 类 号：R73[医药卫生—肿瘤]