FGFR3基因突变在膀胱癌中的诊断价值

Diagnostic value of FGFR3 gene mutation in bladder cancer

目的探讨成纤维细胞生长因子受体3(Fibroblast Growth Factor Receptor 3,FGFR3)基因p.R248C和p.S249C两个突变位点在膀胱癌中的诊断价值。方法收集2019年8月至2020年12月间牡丹江医学院附属红旗医院就诊的40例膀胱癌和40例良性膀胱疾病患者的组织标本,采用硅胶膜离心柱法提取组织中的DNA,利用数字PCR(Digital PCR,dPCR)技术结合MGB荧光探针技术对组织DNA中的FGFR3基因p.R248C和p.S249C两个突变位点进行检测,比较膀胱癌组FGFR3基因两个突变位点与临床参数的关系,分析FGFR3基因两个位点在以上人群的突变情况;应用受试者工作特征(Reciever operating characteristic,ROC)曲线法分析FGFR3基因两个突变位点在膀胱癌中的诊断价值。结果膀胱癌组FGFR3位点p.S249C的突变率为50.00%(20/40),位点p.R248C的突变率为27.50%(11/40),总突变率为57.50%(23/40),与良性膀胱疾病组相比较明显升高,具有统计学意义(P<0.01);FGFR3基因突变在不同年龄组、肿瘤大小、病理分级和术后复发均有统计学意义(P<0.05);ROC曲线显示,FGFR3突变(p.R248C)的AUC为0.638,P=0.034;FGFR3突变(p.S249C)的AUC为0.700,P=0.002,FGFR3总突变的AUC为0.737,P<0.001。结论FGFR3基因位点p.R248C和p.S249C在膀胱癌中有很高的突变率,其中位点p.S249C突变较高,多出现在低级别肿瘤即非肌层浸润性膀胱癌中,是对膀胱癌筛查有意义的突变位点。

Objective FGFR3 was closely related to the occurrence and development of cancer.This study aimed to investigate the diagnostic value of two mutations in bladder cancer in FGFR3 gene p.R248C and p.S249C.Methods 40 cases of bladder cancer and 40 cases of benign bladder tissues were collected in Hongqi Hospital Affiliated to Mudanjiang Medical College from August 2019 to December 2020.The DNA in the tissue was extracted by the silica gel membrane spin column method,and the dPCR technology combined with MGB was used.Fluorescent probe technology were used to detect two point mutations of FGFR3 gene p.R248C and p.S249C in tissue DNA,and the relationship between FGFR3 gene mutation and clinical parameters in the bladder cancer group was compared,and the mutation of FGFR3 gene in the above population were analyzed.The ROC curve method was used to analyze the diagnostic value of FGFR3 gene in bladder cancer.Results The mutation rate of p.S249C at FGFR3 site in the bladder cancer group was 50.00%(20/40),the mutation rate at site p.R248C was 27.50%(11/40),and the total mutation rate was 57.50%(23/40),which was significantly higher than that in the benign bladder disease group with statistical significance(P<0.01).FGFR3 gene mutations were statistically significant in different age groups,tumor sizes,pathological grades,and postoperative recurrence(P<0.05).ROC curve showed that the AUC of FGFR3 mutation(p.R248C)was 0.638,P=0.034;the AUC of FGFR3 mutation(p.S249C)was 0.700,P=0.002;AUC of FGFR3 total mutation was 0.737,P<0.001.Conclusion FGFR3 gene p.R248C and p.S249C had a high mutation rate in bladder cancer,and the p.S249C mutation was relatively high.The meaningful mutant site of bladder cancer was more in non-muscular invasive bladder cancer.