Cytoplasmic Expression of DCLK1-S, a Novel DCLK1 Isoform, Is Associated with Tumor Aggressiveness and Worse Disease-Specific Survival in Colorectal Cancer

Abstract

Isoform-specific function of doublecortin-like kinase 1(DCLK1) has highlighted key role of the DCLK1-S (short isoform) in maintenance, progression, and invasion of tumor. Therefore, this study was designed to produce an anti-DCLK1-S polyclonal antibody in order to specifically evaluate expression pattern and clinical significance of DCLK1-S in a well-defined tissue microarray (TMA) series of colorectal tissues including 348 colorectal cancer (CRC) and 51 adjacent normal tissues during a follow-up period of 108 months. Expression of DCLK1-S was significantly higher in CRC samples compared to adjacent normal samples (P < 0.001). Cytoplasmic expression of DCLK1-S was significantly higher in the tumors at advanced stage of the cancer and with poorer differentiation (P<0.001, P= 0.02). The patients with CRC whose tumors showed higher cytoplasmic expression of DCLK1-S had worse disease-specific survival (DSS) (log-rank test, P = 0.03) and 5-year DSS rates (P= 0.01). Additionally, an improved prognostic value was observed in the patients with CRC with high DCLK1-S expression vs. its moderate expression (HR: 2.70, 95% CI: 0.98-7.38; p =0.04) by multivariate analysis. Our findings strongly supported that high cytoplasmic expression of DCLK1-S compared to its moderate expression could be considered as an independent prognostic factor influencing DSS. Taken together, DCLK1-S can be a promising prognostic candidate and targeted-therapeutic indicator for effective treatment of CRC.