Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2018; 24(37): 4263-4271
Published online Oct 7, 2018. doi: 10.3748/wjg.v24.i37.4263
Potential involvement of heat shock proteins in pancreatic-duodenal homeobox-1-mediated effects on the genesis of gastric cancer: A 2D gel-based proteomic study
Juan Ma, Bei-Bei Wang, Xiao-Yan Ma, Wei-Ping Deng, Li-Shu Xu, Wei-Hong Sha
Juan Ma, Bei-Bei Wang, Wei-Ping Deng, Li-Shu Xu, Wei-Hong Sha, Department of Gastroenterology and Hepatology, Guangdong General Hospital (Guangdong Academy of Medical Sciences), Guangdong Geriatrics Institute, Guangzhou 510080, Guangdong Province, China
Xiao-Yan Ma, Forensic Identification Institute, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, Guangdong Province, China
Author contributions: Ma J and Wang BB contributed equally to this work; Ma J and Sha WH conceived the study; Ma J and Ma XY performed the research; Wang BB and Deng WP analyzed the data; Ma J wrote this manuscript; Xu LS revised this manuscript; Sha WH supervised the report; all authors gave intellectual input to the study and approved the final version of the manuscript.
Supported by Guangdong Natural Science Fund, No. 2016A030313765; and Guangdong medical scientific research fund, No. A2017070 and No. A2017122.
Institutional review board statement: The institutional review board at the Guangdong General Hospital approved the study protocol. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional 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:
Correspondence to: Wei-Hong Sha, MD, PhD, Chief Doctor, Professor, Department of Gastroenterology and Hepatology, Guangdong General Hospital (Guangdong Academy of Medical Sciences), Guangdong Geriatrics Institute, 106 Zhongshan Er Road, Guangzhou 510080, Guangdong Province, China.
Telephone: +86-20-83827812 Fax: +86-20-83827812
Received: May 30, 2018
Peer-review started: May 30, 2018
First decision: July 18, 2018
Revised: August 9, 2018
Accepted: August 24, 2018
Article in press: August 24, 2018
Published online: October 7, 2018
Research background

As one of the homeobox genes that play critical roles in the pattern formation of embryos, pancreatic-duodenal homeobox-1 (PDX1) is widely expressed in Brunner’s glands of the duodenum, pancreatic β cells, and gastric pyloric gland cells. PDX1 plays a key role in the development of the digestive system, including antrum, duodenum, and pancreas. Downregulation of PDX1 has been observed in gastric cancer, which suggests its potential role in gastric tumorigenesis. Nevertheless, the downstream mechanisms that mediate the effect of PDX1 on gastric tumorigenesis are still poorly understood.

Research motivation

Although PDX1 has been found to be involved in gastric tumorigenesis, its downstream regulating mechanism is still unclear.

Research objectives

To clarify the differential protein profile in PDX1-overexpressed gastric cell line and explore functional proteins involved in PDX1-mediated effects on gastric tumorigenesis.

Research methods

A PDX1-overexpressed model was established using gastric cancer cell line SGC7901 (SGC-PDX1). As a method that is still widely used to identify cancer-associated proteins, 2DE-based proteomics was applied to determine the differential protein profile between SGC-PDX1 and SGC-pcDNA. The differential proteins were then subjected to qRT-PCR and immunoblotting for further confirmation. Finally, direct interactions between PDX1 and the identified differential proteins were evaluated by co-immunoprecipitation.

Research results

Seven proteins were found to be differentially expressed in SGC-PDX1 using 2-DE proteomics. Immunoblotting confirmed that the three differential HSPs (HSP70, HSP60, HSP27) were downregulated in SGC-PDX1. However, qRT-PCR analysis identified increased HSP mRNA in SGC-PDX1, which indicates that PDX1 may post-translationally regulate the expression of the HSPs. Further study is warranted to elucidate the relationship of HPS70 and PDX1, as co-immunoprecipitation did not identify direct interaction between them.

Research conclusions

HSPs are involved in PDX1-mediated effects on the genesis of gastric cancer and the interaction between HSP70 and PDX1 is indirect.

Research perspectives

This study demonstrates the involvement of HSPs in PDX1-mediated effects on gastric tumorigenesis. Further study is warranted to elucidate the downstream regulating mechanism of PDX1 on HSPs.