Brief Article
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World J Gastroenterol. Mar 21, 2014; 20(11): 3018-3024
Published online Mar 21, 2014. doi: 10.3748/wjg.v20.i11.3018
Midkine promotes perineural invasion in human pancreatic cancer
Jun Yao, Wen-Yao Li, Shuo-Guo Li, Xiao-Shan Feng, She-Gan Gao
Jun Yao, Wen-Yao Li, Shuo-Guo Li, Xiao-Shan Feng, She-Gan Gao, Department of Oncology, First Affiliated Hospital, Henan University of Science and Technology, Luoyang 471003, Henan Province, China
Author contributions: Yao J and Li WY contributed equally to this work; Yao J, Li SG and Feng XS designed the research; Yao J and Li WY performed the research; Gao SG provided some reagents; Yao J and Li WY analyzed data and wrote the paper.
Supported by National Natural Science Foundation of China, No. U1204819; the Health Science and Technology Innovation Talents Program of Henan Province, No. 4203
Correspondence to: Xiao-Shan Feng, PhD, MD, Professor, Department of Oncology, First Affiliated Hospital, Henan University of Science and Technology, King Wah Road 24, Luoyang 471003, Henan Province, China. yaojun74@163.com
Telephone: +86-379-64815783 Fax: +86-379-64815783
Received: September 16, 2013
Revised: November 14, 2013
Accepted: January 6, 2014
Published online: March 21, 2014
Abstract

AIM: To investigate midkine (MK) and syndecan-3 protein expression in pancreatic cancer by immunohistochemistry, and to analyze their correlation with clinicopathological features, perineural invasion, and prognosis.

METHODS: Pancreatic cancer tissues (including adequately sized tumor tissue samples and tissue samples taken from areas less than 2.0 cm around the tumor) were taken from 42 patients who were undergoing a partial duodenopancreatectomy. MK and syndecan-3 proteins were detected by immunohistochemistry using a standardized streptavidin-peroxidase method, and analyzed for their correlation with clinicopathological features, perineural invasion, and prognosis. Associations of neural invasion with aggressive characteristics of pancreatic cancer and the presence of perineural invasion were assessed by two independent observers blinded to the patient status.

RESULTS: MK and syndecan-3 were found in 26 (61.9%) and 24 (57.1%) specimens, respectively. MK and syndecan-3 expression was associated with perineural invasion (P = 0.018 and 0.031, respectively). High MK expression was closely associated with advanced tumor, node and metastasis stage (P = 0.008), lymph node metastasis (P = 0.042), and decreased postoperative survival at 3 years (51.0% vs 21.8%, P = 0.001). Syndecan-3 levels were correlated with tumor size (P = 0.028). Patients who were syndecan-3 negative had a higher cumulative survival rate than those who were positive, but the difference was not significant (44.0% vs 23.0%, P > 0.05).

CONCLUSION: MK and syndecan-3 are frequently expressed in pancreatic cancer and associated with perineural invasion. High expression of MK and syndecan-3 may contribute to the highly perineural invasion and poor prognosis of human pancreatic cancer.

Keywords: Midkine, Syndecan-3, Pancreatic cancer, Neurite growth, Perineural invasion

Core tip: Midkine (MK) has diverse biological properties, including neuritis outgrowth and tumor progression. Syndecan-3 is a high-affinity receptor for MK and an essential component for neurite outgrowths. MK and its receptor may play an important role during perineural invasion. In this study, MK and syndecan-3 proteins levels were detected and analyzed for correlations with clinicopathological features, perineural invasion, and prognosis. Our results show that high expression of MK contributes to the highly perineural invasion and poor prognosis of human pancreatic cancer.