Abstract: The DOC-2/DAB2 interactive protein (DAB2IP) is a novel member of the Ras GTPase-activating protein family, and its downregulation is an unfavorable prognostic factor in several human malignancies. In this study, we retrospectively analyzed clinicopathological features, outcomes, and DAB2IP expression in 77 patients with urothelial carcinoma of the bladder (UCB). Expression of DAB2IP and p-STAT3 was examined in tumors and in matched adjacent non-cancerous tissues, using immunohistochemistry. We found a marked reduction in the expression of DAB2IP in UCB specimens, which was significantly associated with advanced pathological stage (P =0.037), high pathological grade (P =0.016), and muscle invasion (P =0.004). Moreover, multivariate analysis identified DAB2IP as an independent prognostic factor of cancer-specific survival (hazard ratio [HR] =0.23, 95% confidence interval [CI] =0.07–0.78, P =0.018). Most importantly, DAB2IP was negatively correlated with p-STAT3 expression (P =0.009), which predicted a shorter overall survival in patients with UCB (HR =2.68, 95% CI =1.63–6.99, P =0.044). In conclusion, downregulation of DAB2IP is associated with features of biologically aggressive UCB and may be a promising biomarker in patients after radical cystectomy.
Keywords: bladder urothelial carcinoma, DAB2IP, therapy targets, prognosis