Cytoplasmic expression of DCLK1-S, a novel DCLK1 isoform, is associated with tumor aggressiveness and worse disease-specific survival in colorectal cancer
Affiliations: [a] Oncopathology Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran | [b] Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran | [c] Department of Pathology, Hasheminejad Kidney Center, School of Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran | [d] Division of Histology, Department of Basic Sciences, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran | [e] Department of Epidemiology, School of Public Health, Iran University of Medical Sciences, Tehran, Iran
Correspondence:
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Corresponding authors: Zahra Madjd, Oncopathology Research Center, Department of Molecular Medicnie, Iran University of Medical Sciences (IUMS), Tehran, Iran. Tel./Fax: +98 2188622608; E-mails: majdjabari.z@iums.ac.ir and zahra.madjd@yahoo.com. Roya Ghods, Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran. Tel./Fax: +98 2186704837; E-mails: ghods.ro@iums.ac.ir and rghods77@yahoo.com.
Abstract: BACKGROUND: Isoform-specific function of doublecortin-like kinase 1 (DCLK1) has highlighted the key role of the DCLK1-S (short isoform) in the maintenance, progression, and invasion of the tumor. OBJECTIVE: This study was designed to produce an anti-DCLK1-S polyclonal antibody to evaluate DCLK1-S in human colorectal cancer (CRC) specifically. METHODS: The expression pattern and clinical significance of DCLK1-S were assessed in a well-defined tissue microarray (TMA) series of 348 CRC and 51 adjacent normal tissues during a follow-up period of 108 months. RESULTS: 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 the advanced stage of 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. CONCLUSIONS: Our findings strongly supported that high cytoplasmic expression of DCLK1-S compared to its moderate expression could be considered an independent prognostic factor influencing DSS.
