Runt相关转录因子3基因甲基化及细胞核增殖抗原指数与膀胱癌预后的相关性  

Correlation of runt-related transcription factor 3 gene methylation and proliferating cell nuclear antigen index with the prognosis of bladder cancer

作　　者：高义胜 车峰远 孙富广[2] 陆通 张英豪 王志明 刘杰[2] 李敬东[3] Gao Yisheng;Che Fengyuan;Sun Fuguang;Lu Tong;Zhang Yinghao;Wang Zhiming;Liu Jie;Li Jingdong(Graduate School of Guangzhou University of Traditional Chinese Medicine,Guangzhou 510330,China;Department of Urology,Linyi People’s Hospital,Linyi 276002,China;Department of Oncology,Linyi People’s Hospital,Linyi 276002,China)

机构地区：[1]广州中医药大学研究生院,510330 [2]临沂市人民医院泌尿外科,276002 [3]临沂市人民医院肿瘤内科,276002

出　　处：《中华实验外科杂志》2022年第3期581-584,共4页Chinese Journal of Experimental Surgery

基　　金：山东省医药卫生科技发展计划项目(2017WSA13016)。

摘　　要：目的探讨Runt相关转录因子3(Runx3)基因甲基化及细胞核增殖抗原(Ki-67)指数与膀胱癌预后的相关性。方法膀胱癌细胞和人膀胱上皮永生化细胞购自中国科学院典型培养物细胞库。研究对象为2016年1月至2018年12月诊治的90例膀胱癌患者。采用甲基化特异性聚合酶链反应(MSP)法检测Runx3基因甲基化,采用免疫组织化学法检测Ki-67指数。比较不同临床病理因素中Runx3基因甲基化和Ki-67指数差异,分析膀胱癌预后与Runx3基因甲基化和Ki-67指数的关系。计数资料采用χ^(2)检验,两组间比较行t检验,多组间比较采用单因素方差分析(组间比较采用SNK检验);生存分析采用Kaplan-Meier模型;危险因素分析采用Cox比例风险模型。结果膀胱癌患者肿瘤组织Runx3基因甲基化及Ki-67指数显著高于癌旁组织[Runx3基因甲基化率为66.7%比18.9%,Ki-67指数为(43.8±2.5)%比(8.7±1.1)%],差异有统计学意义(t或χ^(2)=13.233、24.562,P<0.05)。胱癌细胞(T24、UM-UC-3、5637、RT-112)Ki-67指数显著高于人膀胱上皮永生化细胞(SV-HUC-1)[(51.1±2.9)%、(47.6±2.5)%、(40.4±3.1)%、(45.9±2.6)%比(7.4±1.3)%)],差异有统计学意义(F=42.387,P<0.05)。膀胱癌患者肿瘤组织中Runx3基因甲基化及Ki-67指数在肿瘤直径、病灶数目、肿瘤分级、T分期、N分期和临床分期方面的差异均有统计学意义(Runx3基因甲基化χ^(2)=4.049、5.148、5.553、10.326、7.394、18.159,Ki-67指数t=9.238、8.127、13.197、15.233、18.137、23.475,均P<0.05)。Runx3基因甲基化及Ki-67指数≥(43.8±2.5)%膀胱癌患者中位生存期及3年生存率显著低于Runx3基因未甲基化及Ki-67指数<(43.8±2.5)%患者[中位生存期(13.2±1.4)个月比(24.6±1.7)个月,3年生存率12.6%比41.9%,t或χ^(2)=24.191、8.235,P<0.05]。多因素回归分析显示Runx3基因甲基化及Ki-67指数为影响膀胱癌预后的独立危险因素(Runx3基因甲基化风险比为1.793,Ki-67指数风险比为2.094,P<0.05)。结论RObjective To study the correlation of runt-related transcription factor 3(Runx3)gene methylation and proliferating cell nuclear antigen(Ki-67)index with the prognosis of bladder cancer.Methods Bladder cancer cells and human bladder epithelial immortalized cells were purchased from Cell Bank of the Type Culture Collection.Totally,90 bladder cancer patients diagnosed and treated from Jan.2016 to Dec.2018 were chosen for study.The methylation of Runx3 gene was detected by methylation specific polymerase chain reaction(MSP),and the Ki-67 index was detected by immunohistochemistry.The differences in Runx3 gene methylation and Ki-67 index among different clinicopathological factors were compared,and the relationship between the prognosis of bladder cancer and Runx3 gene methylation and Ki-67 index was analyzed.The enumeration data were analyzed byχ^(2)test,the comparison between two groups was performed by t test,the comparison among multiple groups was performed by One-way analysis of variance,the Kaplan-Meier model was used for survival analysis,and the Cox proportional hazards model was used for risk factor analysis.Results The Runx3 gene methylation and Ki-67 index in tumor tissues were significantly higher than those in adjacent tissues[Runx3 gene methylation rate:66.7%vs.18.9%;Ki-67 index:(43.8±2.5)%vs.(8.7±1.1)%]with statistically significant differences(t orχ^(2)=13.233,24.562,P<0.05).The Ki-67 index of bladder cancer cells(T24,UM-UC-3,5637,RT-112)was significantly higher than that of SV-HUC-1[(51.1±2.9)%,(47.6±2.5)%,(40.4±3.1)%,(45.9±2.6)%vs.(7.4±1.3)%)]with statistically significant differences(F=42.387,P<0.05).The differences of Runx3 gene methylation and Ki-67 index in tumor tissue of bladder cancer patients in tumor diameter,number of lesions,tumor grade,T stage,N stage and clinical stage were statistically significant(Runx3 gene methylation:χ^(2)=4.049,5.148,5.553,10.326,7.394,18.159;Ki-67 index:t=9.238,8.127,13.197,15.233,18.137,23.475,all P<0.05).The median survival and 3-year survival rates o

关 键 词：膀胱癌 细胞核增殖抗原 预后 

分 类 号：R737.14[医药卫生—肿瘤]