Abstract 4034: DCLK1 is upregulated in melanoma and it is a novel predictive marker for survival and response
Authors: Dongfeng Qu, Nathaniel Weygant, Parthasarathy Chandrakesan, Kamille Pitts, Randal May, Adam Asch, Alexandra Ikeguchi, Courtney Houchen
Journal: Cancer Research (2019)

Abstract Melanoma is the deadliest form of all skin cancer, and the incidence of melanoma has been rising for the last 30 years. There are only a few reported biomarkers for prediction and prognosis for melanoma, therefore, there is an unmet medical need to identify predictive and prognostic biomarkers. Doublecortin-like kinase 1 (DCLK1) marks a population of tumor-initiating cells in colonic and pancreatic cancers, and it is overexpressed in many solid tumors. Our preliminary studies suggest that DCLK1 is overexpressed in serum samples of melanoma patients and it maybe a novel biomarker for melanoma. In this study we examined DCLK1 expression in melanoma tumor tissues and further evaluated whether its levels in serum could be quantitatively assessed in melanoma patients before and after therapy treatment. Immunohistochemistry (IHC) analysis was performed to detect DCLK1 in a tissue microarray with 60 tumor and normal adjacent tissues (NAT) from melanoma patients. ELISA assay were performed to detect DCLK1 levels in the serum samples of melanoma patients before and after treatment. Western blotting was also performed to detect DCLK1 protein in the serum samples of melanoma patients. Additionally, analysis of DCLK1 and correlative gene expressions was performed using TCGA Melanoma dataset. Here we report that the intensity of DCLK1 staining in melanoma tumor tissues are significantly increased compared to NAT. DCLK1 levels in the serum were elevated in melanoma patients (n=65) compared to healthy volunteers. Patients with higher levels of serum DCLK1 had reduced overall survival compared to patients with lower levels of serum DCLK1. We also compared DCLK1 levels in 10 patients for whom pre- and post- treatment samples were available. Among these patients, seven had elevated DCLK1 before treatment and had a significantly decrease (about 30-50%) in serum DCLK after treatment. Three patients had no change in DCLK1 levels after treatment. Interestingly, the patients with decrease level of DCLK1 post-treatment demonstrated significant clinical responses to therapy, however, the patients with no change in DCLK1 level post therapy showed no clinical improvement (p&amp;lt;0.002). Our study suggested that serum DCLK1 may be an independent prognostic factor, and treatment-induced reduction in serum DCLK1 was associated with excellent clinical response. These data taken together suggest that DCLK1 maybe a novel biomarker for melanoma for prognosis and response purposes. Citation Format: Dongfeng Qu, Nathaniel Weygant, Parthasarathy Chandrakesan, Kamille Pitts, Randal May, Adam Asch, Alexandra Ikeguchi, Courtney Houchen. DCLK1 is upregulated in melanoma and it is a novel predictive marker for survival and response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4034.