Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2017; 23(31): 5764-5772
Published online Aug 21, 2017. doi: 10.3748/wjg.v23.i31.5764
Doublecortin and CaM kinase-like-1 as an independent prognostic factor in patients with resected pancreatic carcinoma
Kohei Nishio, Kenjiro Kimura, Ryosuke Amano, Bunzo Nakata, Sadaaki Yamazoe, Go Ohira, Kotaro Miura, Naoki Kametani, Hiroaki Tanaka, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira
Kohei Nishio, Kenjiro Kimura, Ryosuke Amano, Sadaaki Yamazoe, Go Ohira, Kotaro Miura, Naoki Kametani, Hiroaki Tanaka, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira, Department of Surgical Oncology, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka 545-8585, Japan
Bunzo Nakata, Department of Surgery, Kashiwara Municipal Hospital, Kashiwara City, Osaka 582-0005, Japan
Author contributions: Kimura K designed the studies; Nishio K drafted the manuscript; Amano R, Muguruma K, Tanaka H, Yamazoe S, Ohira G, Miura K, Kametani N and Hirakawa K provided support in design and interpretation of the study; Nishio K and Kimura K performed the statistical analyses; Hirakawa K and Nakata B helped in drafting of the manuscript; Ohira M provided overall supervision of the manuscript; all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Osaka City University Institutional Review Board.
Informed consent statement: Written informed consent was obtained from all patients.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kenjiro Kimura, MD, PhD, Senior Lecturer, Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan. kenjiro@med.osaka-cu.ac.jp
Telephone: +81-6-66453838 Fax: +81-6-66466450
Received: March 31, 2017
Peer-review started: April 8, 2017
First decision: April 26, 2017
Revised: May 11, 2017
Accepted: July 22, 2017
Article in press: July 24, 2017
Published online: August 21, 2017
Processing time: 140 Days and 22.4 Hours
Abstract
AIM

To elucidate the effect of expression of doublecortin and CaM kinase-like-1 (DCLK1) in patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS

Tumor specimens were obtained from 136 patients with pancreatic cancer who had undergone resection without preoperative therapy between January 2000 and December 2013 at the Department of Surgical Oncology, Osaka City University. The resected specimens were analyzed for associations with clinicopathological data, including DCLK1 expression, epithelial mesenchymal transition (EMT) marker expression, and cancer stem cell (CSC) marker expression. Univariate and multivariate survival analyses were performed and we assessed the association between DCLK1 expression and clinicopathological factors, including the EMT marker and CSC marker.

RESULTS

In total, 48.5% (66/136) of the pancreatic cancer samples were positive for DCLK1. Patients with DCLK1-positive tumors had significantly shorter survival times than those with DCLK1-negative tumors (median, 18.7 mo vs 49.5 mo, respectively; P < 0.0001). Positive DCLK1 expression correlated with histological grade (P = 0.0290), preoperative CA19-9 level (P = 0.0060), epithelial cell adhesion molecule (EpCAM) expression (P = 0.0235), and the triple-positive expression of CD44/CD24/EpCAM (P = 0.0139). On univariate survival analysis, five factors were significantly associated with worse overall survival: histological grade of G2 to G4 (P = 0.0091), high preoperative serum SPan-1 level (P = 0.0034), R1/2 (P < 0.0001), positive expression of DCLK1 (P < 0.0001) or CD44 (P = 0.0245). On multivariate survival analysis, R1/2 [odds ratio (OR) = 2.019, 95% confidence interval (CI): 1.380-2.933; P = 0.0004] and positive DCLK1 expression (OR = 1.848, 95%CI: 1.2854-2.661; P = 0.0009) were independent prognostic factors.

CONCLUSION

DCLK1 expression was found to be an independent prognostic factor and it may play a crucial prognostic role by promoting acquisition of stemness.

Keywords: Doublecortin and CaM kinase-like-1; Pancreatic cancer; Epithelial mesenchymal transition; Cancer stem cell; Prognostic factor

Core tip: Doublecortin and CaM kinase-like-1 (DCLK1) is a microtubule - associated kinase and has recently attracted much attention as an important cancer stem cell marker. DCLK1 expression is correlated with aggressiveness in various cancers. However, there have been few investigations correlating DCLK1 expression with survival in pancreatic ductal adenocarcinoma (PDAC). PDAC patients with DCLK1-positive tumors had significantly shorter survival times than those with DCLK1-negative tumors. DCLK1 expression was an independent prognostic factor by multivariate survival analysis. Furthermore, DCLK1-positive expression was correlated to EpCAM expression and triple-positive expression of CD44/CD24/EpCAM. These findings suggest DCLK1 may have a crucial prognostic role in acquisition of stemness.