Abstract
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. This study was designed to produce an anti-DCLK1-S polyclonal antibody to evaluate DCLK1-S in human colorectal cancer (CRC) specifically. 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. 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. 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.
Highlights
Oncogenic role of doublecortin-like kinase 1 (DCLK1) as a putative cancer stem cell (CSC) marker has been clarified in colorectal cancer (CRC)
Our findings strongly supported that DCLK1-S isoform may play a crucial role in invasion, tumor aggressive behavior, and worsened disease-specific survival (DSS) of the patients with CRC
High cytoplasmic expression of DCLK1-S compared to moderate expression could be considered as an independent prognostic factor influencing DSS
Summary
Oncogenic role of doublecortin-like kinase 1 (DCLK1) as a putative cancer stem cell (CSC) marker has been clarified in colorectal cancer (CRC). Radiotherapy, chemotherapy, and targeted therapy are used as the current treatment for the patients with CRC. Combining these traditional methods with new targeted-therapy strategies could increase survival rate of the patients with CRC [2]. Considering crucial role of cancer stem cells (CSCs) in tumorigenesis, tumor invasion, and drug-resistance, many efforts have been made to discover specific markers in order to target CSCs in various cancers including CRC [3,4,5,6]. Among various markers used for identification of CRC-CSCs, doublecortin-like kinase 1 (DCLK1), as a putative CSC marker has been shown to have a crucial oncogenic role in various in-vivo and in-vitro experiments, in pancreatic and colon cancers [5, 7,8,9,10] so that, DCLK1 is called as a well-known CRC-CSC marker distinguished cancer cells from normal cells in Apc Min/+ mice [7]
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