Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2019; 25(17): 2086-2098
Published online May 7, 2019. doi: 10.3748/wjg.v25.i17.2086
Analysis of the autophagy gene expression profile of pancreatic cancer based on autophagy-related protein microtubule-associated protein 1A/1B-light chain 3
Yan-Hui Yang, Yu-Xiang Zhang, Yang Gui, Jiang-Bo Liu, Jun-Jun Sun, Hua Fan
Yan-Hui Yang, Yang Gui, Jun-Jun Sun, Department of Hepatobiliary Surgery, First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471000, Henan Province, China
Yu-Xiang Zhang, Department of Urology Surgery, First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471000, Henan Province, China
Jiang-Bo Liu, Department of General Surgery, First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471000, Henan Province, China
Hua Fan, First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang 471000, Henan Province, China
Author contributions: Yang YH, Sun JJ and Fan H designed the research; Zhang YH and Gui Y performed the research; Liu JB contributed novel reagents; Fan H analyzed the data; Yang YH, Zhang YX and Gui Y wrote the paper; Fan H and Yang YH performed critical revision of the manuscript.
Supported by the National Natural Science Foundation of China, No. U1504815 and No. U1504808.
Institutional review board statement: The study was reviewed and approved by the First Affiliated Hospital of Zhengzhou University Institutional Review Board.
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Data sharing statement: No additional unpublished data are available.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/
Corresponding author: Hua Fan, PhD, Academic Fellow, First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, No. 24 Jing-Hua Road, Luoyang 471003, Henan Province, China. fanhua19851229@haust.edu.cn
Telephone: +86-379-64830681 Fax: +86-379-64830681
Received: January 9, 2019
Peer-review started: January 10, 2019
First decision: February 26, 2019
Revised: March 20, 2019
Accepted: April 10, 2019
Article in press: April 10, 2019
Published online: May 7, 2019
Processing time: 116 Days and 16.9 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 present, more and more studies have found that autophagy is closely related to the occurrence, development, differentiation and prognosis of pancreatic cancer. Autophagy-related protein microtubule-associated protein 1A/1B-light chain 3 (LC3), as a key protein in the autophagy process, is involved in the formation of the autophagosome. A study by our research group found that high expression of LC3 in pancreatic cancer was positively correlated with neural invasion and poor prognosis. With the development of genomics, gene expression microarray technology, proteomics and bioinformatics, the ability to manipulate and characterize human genes and their products has been acquired. Disease-related genes have been studied at the molecular level to understand the pathogenesis of diseases. On the basis of previous studies and using LC3 as a guidance index, the autophagy gene expression profile of pancreatic cancer was analyzed to guide the functional annotation of differentially expressed genes and to enhance the reliability of bioinformatics prediction and analysis. Thus, to provide a basis for the study of the molecular mechanism of autophagy in pancreatic cancer.

Research motivation

This study focused on the differentially expressed genes based on LC3 to analyze the gene expression profile of autophagy in pancreatic cancer. Thus, to provide a basis for the study of the molecular mechanism of autophagy in pancreatic cancer.

Research objectives

To identify differentially expressed genes in autophagy of pancreatic cancer and to provide a basis for exploring the molecular mechanism of autophagy of pancreatic cancer cells and finding new targets for diagnosis and treatment of pancreatic cancer.

Research methods

On the basis of previous studies and using LC3 as a guidance index, differentially expressed genes involved in the autophagy of pancreatic cancer were identified by a gene expression microarray technique. Protein interaction networks were constructed and the functional clustering of differentially expressed genes was carried out. Key interacting proteins or genes between modules were screened and evaluated by statistical methods, and the pathogenesis of pancreatic cancer was explored.

Research results

After removing genes that are clearly defined in the GENE database, 347 differentially expressed genes were obtained. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed a highly significant new pathway, hsa04216 (ferroptosis), a new cell death pattern associated with iron death. The ubiquitin C (UBC) as a pivot of module interactions, connected several modules related to cancer and autophagy and plays an important role in multiple cell death modules related to autophagy.

Research conclusions

In this study, we identified differentially expressed genes based on the LC3 to analyze the gene expression profile of autophagy in pancreatic cancer. Three hundred and forty-seven genes that have no confirmed association with the autophagy process of human pancreatic cancer cells in previous studies were concentrated, and the key pathways involved in autophagy were enriched. Furthermore, a key gene UBC which is closely related to the occurrence of perineural invasion (PNI) was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through UBC.

Research perspectives

With the development of genomics, gene expression microarray technology, proteomics and bioinformatics, we have been able to study disease-related genes at the molecular level to understand the pathogenesis of disease, thus to seek new research directions or to find new targets for clinical diagnosis and treatment. In this study, LC3 was used as a target to explore the differential genes related to autophagy in pancreatic cancer cells. Three hundred and forty-seven genes that have no confirmed association with the autophagy process of human pancreatic cancer cells in previous studies were concentrated, it is obviously unrealistic to analyze all the genes interacting with LC3 in vitro. Nevertheless, a key gene UBC which is closely related to the occurrence of PNI was determined. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. Suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through UBC. Therefore, we have planned to supplement some vitro and vivo experiments to further analysis the relationship between them and explore the molecular mechanism of phagocytosis in pancreatic cancer cells.