解整合素金属蛋白酶12在膀胱癌中表达及意义  

Expression and significance of ADAM12 in bladder cancer

作　　者：张晓林 汪盛[1] ZHANG Xiao-lin;WANG Sheng(Department of Urology,the First Affiliated Hospital of Bengbu Medical College,Bengbu 233030,China)

机构地区：[1]蚌埠医学院第一附属医院泌尿外科,安徽蚌埠233000

出　　处：《海南医学院学报》2023年第18期1401-1410,共10页Journal of Hainan Medical University

基　　金：安徽省自然科学基金(1808085MH293)。

摘　　要：目的:探究解整合素金属蛋白酶12(ADAM12)在膀胱癌中的表达及意义。方法:从TCGA数据库中下载肿瘤和正常样品的转录组、临床数据,分析ADAM12在膀胱癌和正常组织中的表达水平及预后,并分析其与临床相关性。收集本院膀胱癌蜡块标本采用免疫组化方法检测癌与癌旁ADAM12蛋白表达水平。体外实验中,通过转染干扰序列将实验分siNC组及siADAM12组,利用CCK8、Transwell及划痕实验评估敲低ADAM12对膀胱癌细胞增殖、迁移的影响。利用Western Blot检测各组膀胱癌细胞中EMT相关蛋白表达水平。利用生物信息学挖掘ADAM12影响膀胱癌进展的潜在作用机制。结果:ADAM12在膀胱癌组织表达高于正常组织(P<0.05)。对比低表达组,高表达ADAM12预后更差(P=0.007),且与肿瘤分期、浸润深度及淋巴结转移等相关(P<0.05)。免疫组化结果表明ADAM12在膀胱癌组织中表达高于邻近组织(P<0.05)。体外实验结果表明,与对照组相比,敲低ADAM12可抑制膀胱癌细胞增殖、迁移(P<0.05)。Western Blot检测结果显示,对比NC组,siADAM12组E⁃cadherin表达增加,N⁃cadherin及Vimentin表达下降;过表达则结果相反。生物信息学分析表明ADAM12可能参与多种癌症相关信号通路且与多种免疫细胞浸润有关(P<0.05)。结论:ADAM12在膀胱癌组织中高表达并与肿瘤免疫细胞浸润相关,并通过调控EMT促进膀胱癌细胞迁移,可能为膀胱癌预后标志物和生物治疗靶点。Objective:To investigate the expression and significance of ADAM12 in bladder cancer.Methods:Transcrip⁃tome data and clinical data of bladder cancer and normal samples from TCGA database were downloaded to analyze the expression level and prognosis of ADAM12 in bladder cancer and normal tissues,and analyze its clinical correlation.Bladder cancer wax block samples were collected to detect the expression level of ADAM12 protein in cancer and adjacent cancer by immunohisto⁃chemistry.In vitro experiments,the experiments were divided into siNC group and siADAM12 group by transfection interference sequence,and the effect of knockdown ADAM12 on the proliferation and migration of bladder cancer cells was evaluated by CCK8,Transwell and scratch experiments.Western Blot was used to detect the expression level of EMT⁃related protein in each group of bladder cancer cells.Bioinformatics was used to explore the potential mechanism of ADAM12 in influencing the progression of bladder cancer.Results:ADAM12 expression in bladder cancer tissue is higher than normal tissue(P<0.05).Compared with the low⁃expression group,the prognosis of high⁃expression ADAM12 was worse(P=0.007),and it was related to tumor stage,depth of invasion and lymph node metastasis(P<0.05).The immunohistochemical results showed that ADAM12 was ex⁃pressed higher in bladder cancer tissues than in neighboring tissues(P<0.05).The results of in vitro experiments showed that knocking down ADAM12 could inhibit the proliferation and migration of bladder cancer cells compared with the control group.Compared with the NC group,the Western Blot test results showed that the expression of E⁃cadherin was increased in the siAD⁃AM12 group,while the expression of N⁃cadherin and Vimentin was decreased.Overexpression leads to the opposite.Bioinformat⁃ics analysis showed that ADAM12 may be involved in multiple cancer⁃related signaling pathways and is associated with the infiltra⁃tion of various immune cells(P<0.05).Conclusion:ADAM12 is highly expressed in bl

关 键 词：ADAM12 膀胱癌 肿瘤转移 EMT 免疫浸润 

分 类 号：R737.14[医药卫生—肿瘤]