Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2017; 23(40): 7232-7241
Published online Oct 28, 2017. doi: 10.3748/wjg.v23.i40.7232
Relationship between autophagy and perineural invasion, clinicopathological features, and prognosis in pancreatic cancer
Yan-Hui Yang, Jiang-Bo Liu, Yang Gui, Liang-Liang Lei, Shui-Jun Zhang
Yan-Hui Yang, Shui-Jun Zhang, Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Yan-Hui Yang, Yang Gui, Department of Hepatobiliary Surgery, First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471000, Henan Province, China
Jiang-Bo Liu, Liang-Liang Lei, Department of General Surgery, First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471000, Henan Province, China
Shui-Jun Zhang, Henan Key Laboratory of Digestive Organ Transplantation, Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou Key Laboratory of Hepatobiliary Pancreatic Diseases and Organ Transplantation, Zhengzhou 450052, Henan Province, China
Author contributions: Yang YH and Liu JB contributed equally to this work; Yang YH and Liu JB performed the majority of the experiments and critically revised the manuscript; Gui Y and Lei LL assisted with various experiments and helped to analyze the data; Zhang SJ and Liu JB drafted and edited the manuscript.
Supported by the National Natural Science Foundation of China, No. U1504815.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of the First Affiliated Hospital of Zhengzhou University.
Conflict-of-interest statement: The authors declare no competing interests.
Data sharing statement: No additional unpublished data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Shui-Jun Zhang, MD, PhD, Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China. zhangshuijun@zzu.edu.cn
Telephone: +86-371-66964992 Fax: +86-371-66964992
Received: July 2, 2017
Peer-review started: August 17, 2017
First decision: August 30, 2017
Revised: September 13, 2017
Accepted: September 20, 2017
Article in press: September 19, 2017
Published online: October 28, 2017
Abstract
AIM

To investigate the relationship between autophagy and perineural invasion (PNI), clinical features, and prognosis in patients with pancreatic cancer.

METHODS

Clinical and pathological data were retrospectively collected from 109 patients with pancreatic ductal adenocarcinoma who underwent radical resection at the First Affiliated Hospital of Zhengzhou University from January 2011 to August 2016. Expression levels of the autophagy-related protein microtubule-associated protein 1A/1B-light chain 3 (LC3) and PNI marker ubiquitin carboxy-terminal hydrolase (UCH) in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, PNI, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis.

RESULTS

In 109 cases of pancreatic cancer, 68.8% (75/109) had evidence of PNI and 61.5% (67/109) had high LC3 expression. PNI was associated with lymph node metastasis, pancreatitis, and CA19-9 levels (P < 0.05). LC3 expression was related to lymph node metastasis (P < 0.05) and was positively correlated with neural invasion (P < 0.05, r = 0.227). Multivariate logistic regression analysis indicated that LC3 expression, lymph node metastasis, pancreatitis, and CA19-9 level were factors that influenced neural invasion, whereas only neural invasion itself was an independent factor for high LC3 expression. Univariate analysis showed that LC3 expression, neural invasion, and CA19-9 level were related to the overall survival of pancreatic cancer patients (P < 0.05). Multivariate COX regression analysis indicated that PNI and LC3 expression were independent risk factors for poor prognosis in pancreatic cancer (P < 0.05).

CONCLUSION

PNI in patients with pancreatic cancer is positively related to autophagy. Neural invasion and LC3 expression are independent risk factors for pancreatic cancer with a poor prognosis.

Keywords: Pancreatic cancer, Perineural invasion, Autophagy, Clinical pathological features, Prognosis

Core tip:The relationship between autophagy and perineural invasion (PNI) was explored for the first time in pancreatic cancer. Pancreatic cancer PNI is related to microtubule-associated protein 1A/1B-light chain 3 (LC3) expression-determined autophagy. PNI and LC3 expression were independent prognostic factors in pancreatic cancer. There might be a special association between autophagy and PNI, which contributes to pancreatic cancer progression. This study might provide a new insight for the mechanism of PNI in pancreatic cancer.