The Utility Of Combined Detection Multiple Tumor Markers And Urine Cytology In The Diagnosis Of Urothelial Carcinoma

Backgroud: Urothelial carcinoma mainly includes bladder urothelial carcinoma(BC)and upper urinary tract urothelial carcinoma(UTUC),and the biological behavior of urothelial carcinoma is intricated,easy to relapse,infiltration and metastasis,and it is too difficult to diagnosis early and monitoring.The main diagnostic methods are endoscopic examination,which is invasive,high cost,operation complicate and subjective variable.Therefore,the discovery for meaningful tumor markers to early diagnosis of urothelial carcinoma and recurrence monitoring has been a urgent study in international research.The U.S.Food and Drug Administration(FDA)has approved FISH,Immunocyt,BTA,and NMP22 as auxiliary testing methods for bladder urothelial carcinoma,which can be used for diagnosis and follow-up,but these approaches have not yet been widely used in our country,and lack of clinical application data;and there is no in-depth study of tumor markers in the upper urinary tract cancer.Therefore,we chose BTA,BTA-stat,NMP22,SURVIVIN,and urine cytology to diagnose bladder cancer and upper urothelial carcinoma.Objectives: 1.To study the differences between tumor markers in bladder cancer,upper urothelial carcinoma with controls;2.To explore the correlation between tumor markers and malignancy of urothelial carcinoma;3.To evaluate the diagnostic efficacy of each tumor marker for urothelial carcinoma;4.To find the best model for combination detection of tumor markers and urine exfoliation cytology.Methods: 1.A total 157 cases of midstream voided urine samples included urothelial carcinoma group and control group were collected for the detection of urine tumor markers.Each urine sample was approximately 50 ml.The UC group included 61 cases of BC and 44 cases of UTUC.In the control group,there were 52 cases,including 32 symptomatic disease group and 20 healthy individuals.The urinary tract urothelial carcinoma and symptomatic disease group also need extra about 300 ml of the second morning voided urine for urine cytology.2.Collect the relevant clinical characteristics data of every single individual in the group.3.Statistical analysis of the biomarkers and cytology test results.Results: 1.The level of BTA and Survivin is higher in BC and UTUC group(B:P<0.0001,P<0.0001,respectively;S: P<0.0001,P<0.05,respectively);The positive rate of BTA-stat and NMP22 detection is significant in BC and UTUC(P<0.0001).2.The expression of BTA and positive rate of BTA-stat were positively correlated with the grade and stage of bladder cancer(BTA:LG vs HG:P<0.001,TaT1 vs T2-T4:P=0.007;BTA-stat:LG vs HG:P<0.001,TaT1 vs T2-T4:P=0.002).NMP22 is closely related to the pathological grade of bladder cancer(P<0.0001),and statistically significant in the primary BC group compared recurrent group(P=0.024).3.Among the every single tumor marker,BTA quantitative detection yielded the best diagnostic efficiency in the diagnosis of urothelial carcinoma,The ROC-AUC was 0.8712,and the sensitivity and specificity were 81.9% and 80.77%,respectively.4.The combination of BTA,Survivin and urine exfoliative cytology yielded the best diagnostic efficacy to diagnose urothelial carcinoma,AUC 0.909,sensitivity and specificity were 76.19%,92.31%,respectively.(95% CI 0.8658-0.954;P<0.0001).Conclusion: BTA,BTA-stat,NMP22,Survivin can be used as potential non-invasive diagnostic molecular markers for urothelial carcinoma,and the combined detection of urinary exfoliative cytology and BTA,Survivin in the diagnosis of urothelial carcinoma is the most valuable model.