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Data sharing statement: No additional unpublished data are available.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
Abstract
BACKGROUND

Pancreatic cancer is a highly invasive malignant tumor. Expression levels of the autophagy-related protein microtubule-associated protein 1A/1B-light chain 3 (LC3) and perineural invasion (PNI) are closely related to its occurrence and development. Our previous results showed that the high expression of LC3 was positively correlated with PNI in the patients with pancreatic cancer. In this study, we further searched for differential genes involved in autophagy of pancreatic cancer by gene expression profiling and analyzed their biological functions in pancreatic cancer, which provides a theoretical basis for elucidating the pathophysiological mechanism of autophagy in pancreatic cancer and PNI.

AIM

To identify differentially expressed genes involved in pancreatic cancer autophagy and explore the pathogenesis at the molecular level.

METHODS

Two sets of gene expression profiles of pancreatic cancer/normal tissue (GSE16515 and GSE15471) were collected from the Gene Expression Omnibus. Significance analysis of microarrays algorithm was used to screen differentially expressed genes related to pancreatic cancer. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to analyze the functional enrichment of the differentially expressed genes. Protein interaction data containing only differentially expressed genes was downloaded from String database and screened. Module mining was carried out by Cytoscape software and ClusterOne plug-in. The interaction relationship between the modules was analyzed and the pivot nodes between the functional modules were determined according to the information of the functional modules and the data of reliable protein interaction network.

RESULTS

Based on the above two data sets of pancreatic tissue total gene expression, 6098 and 12928 differentially expressed genes were obtained by analysis of genes with higher phenotypic correlation. After extracting the intersection of the two differential gene sets, 4870 genes were determined. GO analysis showed that 14 significant functional items including negative regulation of protein ubiquitination were closely related to autophagy. A total of 986 differentially expressed genes were enriched in these functional items. After eliminating the autophagy related genes of human cancer cells which had been defined, 347 differentially expressed genes were obtained. KEGG pathway analysis showed that the pathways hsa04144 and hsa04020 were related to autophagy. In addition, 65 clustering modules were screened after the protein interaction network was constructed based on String database, and module 32 contains the LC3 gene, which interacts with multiple autophagy-related genes. Moreover, ubiquitin C acts as a pivot node in functional modules to connect multiple modules related to pancreatic cancer and autophagy.

CONCLUSION

Three hundred and forty-seven genes associated with autophagy in human pancreatic cancer were concentrated, and a key gene ubiquitin C which is closely related to the occurrence of PNI was determined, suggesting that LC3 may influence the PNI and prognosis of pancreatic cancer through ubiquitin C.

Keywords: Pancreatic cancer; Autophagy-related protein microtubule-associated protein 1A/1B-light chain 3; Perineural invasion; Gene Ontology analysis; Kyoto Encyclopedia of Genes and Genomes pathway analysis; Ubiquitin C

Core tip: In this study, we identified differentially expressed genes based on the autophagy-related protein microtubule-associated protein 1A/1B-light chain 3 (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 ubiquitin C 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 ubiquitin C.