Combined Detection Of Tumor Markers In Urine For Diagnosis Of Bladder Cancer

Objective:Approximately 380 000 cases of bladder cancer occur around the world each year,and in china bladder cancer is the most common urothelial malignant tumor.Early detection and surveillance to predict recurrence depends on cystoscopy and biopsy,but it is an expensive and invasive procedure,cytology is convenient and noninvasive whereas the sensitivity is not very high,These defects limit the early diagnosis and treatment of bladder cancer.In addition,the high recurrence rate of bladder cancer makes postoperative recurrence surveillance particularly important,but there is still a lack of appropriate means,There is an urgent need for a new detection means that can distinguish tumors with the potential to progress and metastasizethese.Tumor biomarkers are present in the urine,blood and tissues can be determined and indicates the presence of a certain malignancy.Therefore,tumor markers are often used to diagnose a specific tumor,provides prognostic information,evaluates of response to treatment,therefore the detection of tumor biomarkers are increasingly valued and becoming a hot spot of current research.In this study,we used ELISA to detect the expression of NMP22,CD44,CK20,CEACAM1 and BTA markers in the urine of patients with bladder cancer,and to explore the clinical application value of Combined detection of tumor markers in urine for diagnosis of bladder cancer.And provide a theoretical basis for future research to develop a more effective tumor markers kit that can detect bladder cancer.Methods: A total of 84 patients admitted to the Second Hospital of Tianjin Medical University from December 2015 to June 2016 were enrolled in this study.64 patients were diagnosed with bladder urothelial carcinoma according to the final pathology report.20 patients were benign non-tumor urinary tract diseases as controls.The levels of NMP22,CD44,CK20,CEACAM1 and BTA in urine samples were detected by ELISA,and Voided urinary cytology(VUC)were tested with acridine orange fluorescence(AO-F)method.Receiver operating characteristics(ROC)curve was drawn by SPSS19.0 software according to the test results so that the cut-off points of NMP22,CD44,CK20,CEACAM1 and BTA could be determined by Youden index.we analyzed the sensitivity,specificity and the positive predictive value of all the individual and combined examining methods and the Wilcoxon test or Fisher exact test method were using to analyze the relationship between the tumor markers and the clinicopathological features of the patients.Results: There was a significant difference between bladder cancer group and the control group.The concentration of 5 tumor markers in bladder cancer patients was significantly higher than that in the control group.the area under the curve(AUC)of NMP22,BTA,CK20,CD44,CEACAM1 were 0.752、0.820、0.773、0.859、0.724,respectively,Compared with the 6 makers,the sensitivity of NMP22 was 84.3%,but the specificity was only 55%.While the specificity of AO-F was 100%,but its sensitivity was the lowest among the markers.CD44 had the highest AUC of 0.857,which means it had the greatest accuracy in the diagnosis of bladder cancer.When CD44 had a Cut-off value of 348.8pg / ml,the sensitivity was 82.8% and the specificity was 85%.The sensitivity of AO-F to the diagnosis of low-grade bladder cancer was 40%,and the sensitivity to diagnosis of high-grade bladder cancer was 70.5%,the difference was statistically significant(p=0.028).The sensitivity of the AO-F method and CEACAM1 in the detection of bladder cancer increased with the increase of staging of bladder cancer,while the other makers had no significant difference in the diagnostic sensitivity of different grades of bladder cancer.Combined use of BTA+CD44+ CK20 had the highest sensitivity of 96.8%,specificity of 80.0%,better than any other makers.Conclusion: ELISA method for detecting these five tumor markers in urine has clinical value for the diagnosis of bladder cancer.Compared with individual tumor markers,CD44 has the greatest accuracy in the diagnosis of bladder cancer.CEACAM1 is more sensitive to high stage bladder cancer,and the AO-F in in exfoliative urinary cytology is more sensitive to high-grade and high-grade bladder cancer.Combined use of CD44 + CK20 + BTA has high sensitivity and specificity and is superior to other detection methods for bladder carcinoma detection.