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Data sharing statement: No additional unpublished data are available.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
Processing time: 73 Days and 19.1 Hours
ARTICLE HIGHLIGHTS
Research background

Pancreatic cancer is a malignant tumor with a poor prognosis that has almost equal mortality and morbidity in patients. At the time of diagnosis, most pancreatic cancer patients have distant metastasis due to early occult symptoms, a lack of effective screening, and perineural growth characteristics. The incidence of perineural invasion (PNI) in pancreatic cancer is 80%-100% and is an important factor leading to postoperative pancreatic cancer recurrence. PNI evaluation of pancreatic cancer can predict disease recurrence and prognosis after surgery. However, the pathogenesis of PNI has not yet been defined. Autophagy, as a mechanism of avoidance of anoikis in pancreatic cancer, is closely related to the survival of pancreatic cancer cells. Microtubule-associated protein 1A/1B-light chain 3 (LC3) is a typical marker of autophagy. LC3 labeling has been used to evaluate autophagy, and high levels of LC3 expression have been found in pancreatic cancer cells. In addition, a previous study showed that pancreatic cancer cells with PNI have higher levels of autophagy. No study has examined the relationship between autophagy and PNI in pancreatic cancer cells.

Research motivation

The relationship between autophagy and PNI was explored for the first time in pancreatic cancer. Pancreatic cancer PNI is related to 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 new insight into the mechanism of PNI in pancreatic cancer.

Research objectives

This study focused on the relationship between pancreatic cancer cell autophagy and PNI, clinicopathological features, and prognosis. The authors found that autophagy and PNI of pancreatic cancer cells are independent risk factors for adverse prognosis. There is a significant correlation between them, and there may be a pathway between them through which they interact with each other to promote the malignant progression of pancreatic cancer. Controlling the role of autophagy in PNI of pancreatic cancer may improve cancer prognosis, which requires further studies into the molecular mechanisms involved.

Research 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 LC3 and perineural invasion marker ubiquitin carboxy-terminal hydrolase in pancreatic cancer tissues were detected by immunohistochemistry. The correlations among LC3 expression, perineural invasion, and clinical pathological features in pancreatic cancer were analyzed. The patients were followed for further survival analysis.

Research results

In this study, they found that LC3, lymph node metastasis, pancreatitis, and CA199 level were factors that influenced neural invasion, whereas only neural invasion itself was an independent factor of high LC3 expression. Perineural invasion and LC3 expression were independent risk factors for poor prognosis in pancreatic cancer. There is a significant correlation between them.

Research conclusions

This study focused on the relationship between pancreatic cancer cell autophagy and PNI, clinicopathological features and prognosis. The authors found that autophagy and PNI of pancreatic cancer cells are independent risk factors for adverse prognosis. There is a significant correlation between them, and there must be a pathway between them through which they interact with each other to promote the malignant progression of pancreatic cancer. Controlling the role of autophagy in PNI of pancreatic cancer may improve cancer prognosis, which requires further studies into the molecular mechanisms involved.