Increased expression of DCLK1, a novel putative CSC maker, is associated with tumor aggressiveness and worse disease-specific survival in patients with bladder carcinomas

Abstract

Doublecortin-like kinase 1 (DCLK1) has been characterized as a novel potential cancer stem cell (CSC) marker in several types of cancer. It is considered as one of the most specific markers for distinguishing colorectal CSCs from normal stem cells. Yet, there are limited reports on the role of DCLK1 as a putative CSC marker in bladder cancer. Using immunohistochemistry, DCLK1 expression was examined in a well-defined tissue microarray series of 472 bladder cancer tissues. The association between DCLK1 protein expression and clinicopathological features, as well as survival outcomes, was assessed. Our findings showed strong, moderate, and weak DCLK1 expression in 123 (26.1%), 230 (48.7%), and 119 (25.2%) of the bladder cancer specimens, respectively. Higher expression of DCLK1 was significantly associated with increase in histological grade (P ≤ .001), pT stage (P = .014), lamina propria (P = .006), and lamina propria/muscularis (L/M) involvement (P = .014). On multivariate analysis, pT stage (P < .001), histological grade (P = .021), and lamina propria involvement (P = .001) were independent prognostic factors in DCLK1 expression. Moreover, the expression of DCLK1 was found to be an independent marker of poor prognosis for disease- specific survival (DSS) (P = .048) in bladder carcinomas. Our observations showed that DCLK1 expression was associated with more aggressive tumor behavior, more advanced disease, and poorer DSS in patients with bladder carcinomas. However, any potential clinical applications of DCLK1 as a novel target molecule in bladder cancer patients would require further investigations.