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Decreased expression of LKB1 predicts poor prognosis in pancreatic neuroendocrine tumor patients undergoing curative resection

Authors Li D, Zhou Y, Liu Y, Lin Y, Yu M, Lu X, Huang B, Sun Z, Jian Z, Hou B

Received 15 October 2017

Accepted for publication 9 January 2018

Published 6 March 2018 Volume 2018:11 Pages 1259—1265

DOI https://doi.org/10.2147/OTT.S154168

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Professor Jianmin Xu


Dezhi Li,1,* Yu Zhou,1,* Yanhui Liu,2,* Ye Lin,1 Min Yu,1 Xin Lu,1 Bowen Huang,1 Zhonghai Sun,1 Zhixiang Jian,1 Baohua Hou1

1Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pathology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of China

*These authors contributed equally to this work

Background:
Liver kinase B1 (LKB1) is a key regulatory protein of cellular metabolism, proliferation, and polarity. The present study aimed to characterize the expression pattern of LKB1 in pancreatic neuroendocrine tumors (pNETs) and evaluate the relationship between LKB1 expression and prognosis in pNETs.
Patients and methods:
We retrospectively analyzed the pathologic and clinical data of 71 pNET patients who underwent curative surgical resection in Guangdong General Hospital. LKB1 mRNA and protein levels in tumor tissues and paired nontumor tissues were evaluated in 24 patients by quantitative real-time reverse-transcription polymerase chain reaction and Western blot, respectively. Immunohistochemical expression of LKB1 in tumor tissues was detected in all of the 71 patients, and the immunohistochemical expression level was re-coded in two classes (high versus low/negative) and correlated with clinicopathological parameters and survival outcomes. The association between LKB1 expression and clinicopathological characters was evaluated by chi-square test and Student’s t-test. Kaplan–Meier curves and log-rank test were used to analyze the survival outcomes, including overall survival (OS) and disease-free survival (DFS).
Results: Compared to adjacent normal tissues, LKB1 mRNA level and protein expression level in tumor tissues were both increased. The immunostaining of LKB1 was mainly found within the cytoplasm. Overall, 52 of 71 (73.2%) cases were positive for LKB1 protein, which showed either a diffuse staining pattern or a partial staining pattern. Decreased LKB1 expression was correlated with older age (P=0.042), increased Ki-67 index (P=0.004), increased mitotic count (P=0.001), and advanced histologic grade (P=0.001). Moreover, patients with low/negative LKB1 expression had shorter OS and DFS than those with high expression.
Conclusion: Our results suggested that LKB1 expression could be a useful prognostic marker for recurrence and survival in pNET patients who had received curative resection.

Keywords: pancreatic neuroendocrine tumors, liver kinase B1, LKB1, prognosis

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