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. 2017 Aug 21;23(31):5764-5772.
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  1 , Kenjiro Kimura  2 , Ryosuke Amano  1 , Bunzo Nakata  3 , Sadaaki Yamazoe  1 , Go Ohira  1 , Kotaro Miura  1 , Naoki Kametani  1 , Hiroaki Tanaka  1 , Kazuya Muguruma  1 , Kosei Hirakawa  1 , Masaichi Ohira  1
Affiliations

Doublecortin and CaM kinase-like-1 as an independent prognostic factor in patients with resected pancreatic carcinoma

Kohei Nishio et al. World J Gastroenterol. .

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

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Conflict of interest statement

Conflict-of-interest statement: The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Immunohistochemical analysis of doublecortin and CaM kinase-like-1 expression. A: Positive expression; B: Negative expression. DCLK1: Doublecortin and CaM kinase-like-1.
Figure 2
Figure 2
Immunohistochemical analysis of doublecortin and CaM kinase-like-1 expression, and epithelial mesenchymal transition and stem cell markers in pancreatic cancer. All pictures show positive expression for each marker (× 200). A: Snail; B: Vimentin; C: E-cadherin; D: N-cadherin; E: CD24; F: CD44; G: CD133; H: EpCAM. DCLK1: Doublecortin and CaM kinase-like-1; EpCAM: Epithelial cell adhesion molecule.
Figure 3
Figure 3
Overall survival of patients according to doublecortin and CaM kinase-like-1 expression. A: The MST of patients with DCLK1-positive tumors was 18.7 mo; B: That of patients with DLCK1-negative tumors was 49.5 mo. The MST of patients with DCLK1 positivity was significantly shorter than that of patients with DCLK1 negativity (P < 0.0001). DCLK1: Doublecortin and CaM kinase-like-1; MST: Median overall survival time.
Figure 4
Figure 4
Relapse-free survival of patients according to doublecortin and CaM kinase-like-1 expression, excluding patients with macroscopic residual tumor. A: RFS of patients with DCLK1 positivity was 10.2 mo; B: That of patients with DCLK1 negativity was 25.5 mo. Relapse of patients with DCLK1 positivity was significantly shorter than that of patients with DCLK1 negativity (P = 0.0005). DCLK1: Doublecortin and CaM kinase-like-1; RFS: Relapse-free survival.
See this image and copyright information in PMC

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