Evaluation of urinary XIAP as a diagnostic biomarker of carcinoma of urinary bladder.

Abstract

Early diagnosis of carcinoma of the bladder remains a challenge. Urine cytology, as an adjunct to cystoscopy, is less sensitive for low-grade tumors. X-linked inhibitor of apoptosis (XIAP), a negative regulator of apoptotic stimuli and a member of apoptosis family, is frequently activated in bladder carcinoma. Our aim is to investigate the significance of urinary XIAP for the noninvasive diagnosis of transitional cell carcinoma (TCC) of the urinary bladder. We examined urinary XIAP expression in a bladder cancer cell line (T24) and in urine of 28 healthy individuals, 46 patients of nonmalignant disorders, and 117 cases (69 primary and 48 recurrent cases) of histologically proven TCC prior to transurethral resection, by using real-time PCR, and compared it with voided urinary cytology (VUC). XIAP expression was found in T24 cell line and also was found to be significantly higher in the cancer group as compared to the controls (p < 0.001). XIAP messenger RNA (mRNA) expression showed a significant (p < 0.05) association with stage and grade (p < 0.05). XIAP shows the sensitivity of 82.91 % and specificity of 78.38 % (p < 0.001), whereas urine cytology had sensitivity of 66.67 % and specificity of 95.95 % for TCC cases. The combination of XIAP and VUC had better sensitivity (98.2 %) and specificity (92.6 %) than they showed individually (p < 0.001). XIAP mRNA expression did not significantly correlated with the patient's age, sex, and smoking (p > 0.05). Urinary XIAP can be used as a noninvasive diagnostic biomarker for bladder TCC in adjunct to cytology mainly for low-grade non-muscle-invasive tumors.