Serum DCLK1 as a Biomarker for Adenoma and Colorectal Neoplasia Detection in Patients Referred for Colonoscopy

Abstract

Introduction: Doublecortin-like kinase 1 (DCLK1), a putative tumor stem cell marker has been shown to be highly expressed in the stromal and epithelial compartments in colon and pancreatic cancer as well as Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). The aim of this study was to investigate whether DCLK1 can be used as an early diagnostic marker for adenoma detection and colorectal neoplasia in serum. Methods: Consecutive patients referred to the Oklahoma City VA Medical Center for colonoscopy were prospectively enrolled into the study from January to May 2017. Five milliliters (mls) of blood was drawn from each patient prior to colonoscopy. During colonoscopy biopsies were obtained and/or polypectomy was performed if indicated and sent to pathology. Tissue samples were stratified into groups after microscopic analysis; normal (n=13), hyperplastic polyp (HP; n=25), tubular adenoma (TA; n=80), tubular adenoma with high-grade dysplasia and colorectal adenocarcinoma (HGD and CRC; n=4). DCLK1 expression in serum was determined by ELISA and correlated with histopathology findings. Results: The study population consisted of 122 patients with mean age of 63.4 years; 94.3% were male. Majority (79.4%) were Caucasian. Increased expression of DCLK1 was found in the serum of patients in the HGD/CRC group compared to the other groups (normal, HP and TA; P=0.006). Increased expression of DCLK1 was also found in the serum of patients with diabetes (P=0.01). After controlling for diabetes, the difference in serum DCLK1 levels among the 4 histologic groups remained (p =0.0002). There was no association between serum DCLK1 expression and age, gender, ethnicity, BMI, tobacco use, alcohol use, personal or family history of colon polyps and/or CRC, polyp size, total polyp burden, or history of other GI cancers (all P>0.05), suggesting that DCLK1 expression in serum is independent of established risk factors for colon polyps and CRC. Conclusion: DCLK 1 may represent a novel molecular marker for detection of adenoma and CRC in serum. However, our results need to be interpreted with caution given the small number of patients in the HGD/CRC group. Enrollment of more patients in the normal and HGD/CRC groups will provide more robust results.Table: Table. Serum DCLK1 Concentration (ELISA) ng/mlFigure: Serum DCLK1 expression level by histology group.