FGFR3和PIK3CA基因突变影响膀胱癌的预后

Effects of FGFR3 and PIK3CA mutations on prognosis of bladder carcinoma

背景与目的:成纤维细胞生长因子受体3(fibroblast growth factor receptor 3,FGFR3)和磷脂酰肌醇3-激酶催化亚基ɑ(phosphoinositide 3 kinase catalytic alpha polypeptide,PIK3CA)基因突变与多种肿瘤的发生、发展密切相关。然而,其临床病理意义尚未明确。探讨FGFR3和PIK3CA基因突变对膀胱癌预后的影响。方法:采用Sanger基因测序技术分析于南京中医药大学张家港附属医院行手术治疗的63例膀胱癌患者中FGFR3(外显子7、10、15)和PIK3CA(外显子9、20)基因突变,同时采用免疫组织化学方法检测FGFR3和PIK3CA蛋白水平。分析FGFR3和PIK3CA基因突变与各临床参数的关系,应用Kaplan-Meier方法进行生存分析,通过多因素COX模型回归分析方法对影响膀胱癌预后的因素进行分析。结果:FGFR3基因突变率为17.46%(11/63),蛋白表达率为33.33%(21/63),PIK3CA基因突变率为7.93%(5/63),蛋白表达率为55.56%(35/63)。FGFR3基因突变与年龄、肿瘤是否复发显著相关(P<0.05),PIK3CA基因突变与各临床参数均无显著相关性(P>0.05);11例FGFR3mut中2例PIK3CAmut,52例FGFR3wt中3例PIK3CAmut,两者比较,差异有统计学意义(χ2=4.61,P=0.03)。FGFR3基因突变型和野生型的无进展生存期(progression-free survival,PFS)分别为29.13和46.25个月,差异有统计学意义(P=0.021),而两组的总生存期(overall survival,OS)差异无统计学意义(P>0.05);PIK3CA基因突变型和野生型比较OS和PFS,差异均无统计学意义(P>0.05)。多参数COX回归分析影响膀胱癌的因素中,FGFR3和PIK3CA基因突变和蛋白表达均不是影响OS的主要因素,病理学分级是影响OS的主要因素,吸烟史和FGFR3基因突变则是影响PFS的主要因素。结论:FGFR3基因突变是膀胱癌预后的不利因素,PIK3CA更易在FGFR3突变的膀胱癌中突变,可能促进FGFR3突变型膀胱癌的恶性行为。

Background and purpose:Alterations in fibroblast growth factor receptor 3(FGFR3)and phosphoinositide 3 kinase catalytic alpha polypeptide(PIK3CA)have been implicated in the pathogenesis of various carcinomas.However,clinicopathological significances have not been clearly established.The aim of our study was to investigate the mutation of FGFR3 and PIK3CA to analyze the prognostic and predictive significance in bladder cancer.Methods:Study cohorts included 63 cases of bladder carcinoma who received surgical treatment in the Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine.The mutation status and overexpression of FGFR3 and PIK3CA were investigated.The findings were analyzed for the association with relevant clinicopathological findings.Kaplan-Meier method was used in survival analysis.Multivariate COX model was used to analyze the factors that might affect the prognosis of bladder carcinoma.Results:Of 63 patients,FGFR3 mutations were found in11 patients(17.46%),and FGFR3 protein overexpression was observed in 21 patients(33.33%);PIK3CA mutations were found in 5 patients(7.93%),and 35 patients had overexpression of PIK3CA protein(55.56%).FGFR3 mutations were correlated with a pattern of different age and recurrence,while PIK3CA mutation was not associated with the relevant clinicopathological parameters.There were 2 PIK3CAmut in 11 cases of FGFR3mut and 3 PIK3CAmut in 52 cases of FGFR3wt(P<0.05).Kaplan-Meier survival analysis showed there was no significant difference in overall survival(OS)and progression-free survival(PFS)between patients with and without PIK3CA mutations.FGFR3 mutations were significantly correlated with shorter PFS,but had no significant influence on OS.Multivariate COX proportional hazards model analysis of OS and PFS showed FGFR3 and PIK3CA mutations were not independent predictors of OS,whereas FGFR3 mutations and smoking were independent predictors of PFS.Conclusion:FGFR3 mutation is an adverse prognostic factor.PIK3CA mutation is more frequent in bladder neoplasm with FGFR3 mutation,which contributes to the malignant behavior of FGFR3 mutant bladder neoplasm.