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. 2020 Sep 1;13(9):2249-2258.
eCollection 2020.

Divergent expression of DCLK1 in gastrointestinal neuroendocrine tumors and primary hepatic, gallbladder, and pancreatic neuroendocrine tumors

Mengjiao Fan  1 , Huan Yan  1 , Miaomiao Gou  1 , Niansong Qian  1 , Guanghai Dai  1
Affiliations

Divergent expression of DCLK1 in gastrointestinal neuroendocrine tumors and primary hepatic, gallbladder, and pancreatic neuroendocrine tumors

Mengjiao Fan et al. Int J Clin Exp Pathol. .

Abstract

Doublecortin-like kinase 1 (DCLK1) is reported to be a negative prognostic marker in colorectal cancer and is involved in tumorigenesis and progression through several miRNA pathways. In this study, We analyzed its expression in neuroendocrine tumor (NET) and explored its relation with survival outcome. 122 patients were enrolled in the study, including 60 cases of GI-NETs, 24 cases of primary hepatic NETs (PHNETs), 16 cases of gallbladder NETs (GBNETs) and 22 cases of pancreatic NETs (pNETs). IHC was performed for DCLK1 on tumor tissue. All patients underwent a baseline visit, histologic determination, and a follow-up for survival. In the 60 cases of GI-NETs, DCLK1 showed diffuse cytoplasmic expression. The positive rates of DCLK1, Syn and CgA were 100% (60/60), 100% (60/60) and 36.7% (22/60), respectively. However, DCLK1 showed negative staining in all of the 62 cases of PHNETs, GBNETs, and pNETs. The mean score of DCLK1, Syn, and CgA were (5.77±2.012), (5.13±2.078) and (2.68±2.797), respectively. DCLK1 was correlated with primary site (P<0.001) and Syn expression (P = 0.045). Additionally, in GI-NETs, we found that DCLK1 expression was associated with worse OS (log-rank = 5.212, P = 0.022). The divergent expression of DCLK1 in NETs suggests different functional roles of DCLK1 in different locations of NET within the digestive system. However, with the limited number of tumor samples, its outcome prediciton still needs further investigation. DCLK1 expression may aid in the diagnosis and prognosis of GI-NETs.

Keywords: Doublecortin-like kinase 1; carcinoid; neuroendocrine tumor; prognosis.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Expression of DCLK1 in NET tissue specimens. Note the negative expression of DCLK1 in PHNET (A, D), GBNET (B, E) and pNET (C, F) patients.
Figure 2
Figure 2
Representative immunohistochemical staining of DCLK1. Note the high cytoplasmic immunoreactivity of DCLK1 in tumor cells but not in surrounding stroma. DCLK1 in gastric NET (A, D), colonic NET (B, E) and rectal NET (C, F) patients.
Figure 3
Figure 3
Pearson analysis comparing DCLK1 and Syn or CgA expression.
Figure 4
Figure 4
Kaplan-Meier analysis of DFS and OS in GI-NETs according to DCLK1 expression in GI NETs.
Figure 5
Figure 5
Kaplan-Meier analysis of OS in G-NET patients and intestinal tract NET patient groups.
See this image and copyright information in PMC

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