Predictive value of combined application with multiple molecular markers in the prognosis of bladder urothelial carcinoma / 国际外科学杂志

ABSTRACT

Objective:Assessing the prognosis of patients with bladder urothelial carcinoma by using multiple molecular markers [epithelial-cadherin (E-cadherin), fibroblast growth factor receptor 3 (FGFR3), Jagged2, Survivin and stromal antigen 2 (STAG2)] in combination method, and compared it with the traditional method of evaluating prognosis by clinical pathological parameters.Methods:Retrospective analysis of 128 cases of bladder urothelial carcinoma patients admitted to Beijing Friendship Hospital, Capital Medical University from January 2010 to December 2016, including 102 males and 26 females; the median age was 70.5 years, ranged from 41 to 93 years. E-cadherin, FGFR3, Jagged2, Survivin and STAG2 alterations by immunohistochemistry during the first surgical treatment. The Kaplan-Meier survival curve was used to evaluate the relationship between the above markers and overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), and clinicopathological indicators of tumors. Use Cox regression model to find the most suitable molecular markers for judging the prognosis of bladder urothelial carcinoma, and compare it with the traditional clinical staging + pathological grading method to evaluate OS to detect its sensitivity and specificity.Results:After 36.4 months of follow-up, it was found that the expressions of E-cadherin, FGFR3, Jagged2 and Survivin were all related to the OS, RFS and PFS of bladder urothelial carcinoma (all P<0.05). The expression of STAG2 was related to the TMN stage of bladder urothelial carcinoma ( P=0.047) and pathological grade ( P=0.015). Cox regression analysis showed that Survivin ( P=0.001) and Jagged2 ( P=0.037) were independent risk factors for evaluating the OS of bladder urothelial carcinoma, and Survivin ( P<0.001) and Jagged2 ( P=0.006) were independent risk factors for RFS, Survivin ( P=0.001) was also an independent risk factor for PFS. Multivariate analysis of the above molecular markers showed that the prognosis of patients with more than 3 molecular markers was better than that of independent application or the use of two of them to evaluate the prognosis ( P<0.001). The combined application of Survivin and Jagged2 to evaluate the 5-year survival rate was not less sensitive and specific than the clinical and pathological indicators (93.5% vs 77.2%, 84.7% vs 81.3%). Conclusions:Five molecular markers of E-cadherin, FGFR3, Jagged2, Survivin and STAG2 have an evaluation effect on the prognosis of bladder urothelial carcinoma, and some can independently predict the OS and RFS of patients with bladder urothelial carcinoma, however, the combined application is better than the single molecular marker to evaluate the prognosis. Compared with the traditional method of evaluating the prognosis by clinical pathological parameters, the combined application of Jagged2 and Survivin may be a better choice for evaluating the prognosis of patients with bladder urothelial carcinoma.