Increased Expression of DCLK1 in Bladder Cancer and its Correlation with Tumor Aggressiveness and poor prognosis

Background: Cancer stem cell (CSC) based gene expression signatures are associated with tumor initiation, progression, and matastasis in various tumor types. Doublecortin-like kinase 1 (DCLK1) has been characterized as a novel specific colorectal Cancer Stem Cell (CSC) that can distinguish colorectal CSCs from normal stem cells (NSCs). Hence, the current study was designed to investigate the expression levels of DCLK1 and its clinical significance in bladder cancer patients.Materials and methods: Using immunohistochemistry, DCLK1 expression was examined in a well-defined tissue microarray (TMA) series of 516 bladder cancer tissues and 29 normal adjacent tissues. The correlation of DCLK1 expression with clinicopathologic parameters was also assessed. Results: Among 516 bladder cancer cases; strong, moderate, and weak immunohistochemical expression of DCLK1 was detected in 139 (27%), 252 (48.8%), and 125 (24.2%), respectively, while 75% of normal tissues showed lower DCLK1 immunoreactivity. Lower DCLK1 expression was observed in 64.2% of low grade and 50% of high grade tumors. Conversely, higher DCLK1 expression was found in 35.8% of low grade and 50% of high grade tumors. Univariate analysis showed a significant direct correlation between DCLK1 expression with tumor grade (P≤ 0.001), tumor size (P=0.01), lamina propria involvement (P< 0.001) muscularis invasion (P< 0.001) and lamina propria/muscularis (L/M) involvement (P-value < 0.001).Conclusion: Our observation showed higher levels of DCLK1 expression in more aggressive bladder carcinomas. This provides support for the assertion that DCLK1 plays a role in tumorigenesis, aggressiveness, migration, and metastasis in bladder cancer. However, clinical applications of DCLK1 as a novel target molecule in bladder cancer patients would require further mechanistic characterization and clinical evaluation.

Keywords:

Bladder cancer , Cancer Stem cell , DCLK1