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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: Dr Jianmin Xu
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