Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2020; 26(1): 21-34
Published online Jan 7, 2020. doi: 10.3748/wjg.v26.i1.21
Feedback regulation between phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 and transforming growth factor β1 and prognostic value in gastric cancer
Qi Shao, Zhi-Ming Chen
Qi Shao, Zhi-Ming Chen, Department of Chemotherapy/Radiotherapy, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu Province, China
Author contributions: Shao Q conducted the experiments and data analysis and drafted the manuscript; Chen ZM designed the project and revised the manuscript.
Institutional review board statement: This study was approved by the Ethics Committee of Affiliated Hospital of Nantong University.
Institutional animal care and use committee statement: This study does not include the animal experiments, so the institutional animal care use statement is not applicable to this manuscript.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: The bioinformatic data comes from the public databases, and 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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Zhi-Ming Chen, MSc, Doctor, Department of Radiotherapy, Affiliated Hospital of Nantong University, No. 10 Xisi Road, Nantong 226001, Jiangsu Province, China. czm614@163.com
Received: November 26, 2019
Peer-review started: November 26, 2019
First decision: December 12, 2019
Revised: December 15, 2019
Accepted: December 22, 2019
Article in press: December 22, 2019
Published online: January 7, 2020
Processing time: 41 Days and 13.5 Hours
ARTICLE HIGHLIGHTS
Research background

Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 (PREX1) is considered a pro-oncogene is some cancer types and is involved in some common cancer-promoting pathways, such as phosphatidylinositol 3-kinase/AKT and MEK/ERK. However, its expression and clinical value in gastric cancer has not been reported. Gastric cancer is a common high mortality disease, and identifying a novel therapeutic target could be valuable.

Research motivation

The goal was to confirm the expression of PREX1 in gastric cancer tissues and to correlate PREX1 level and disease development. The potential mechanism of PREX1 in the regulation of transforming growth factor (TGF) β pathway was also examined.

Research objectives

To evaluate the level and clinical value of PREX1 in the gastric cancer and to determine the potential mechanism in the regulation of gastric cancer metastasis.

Research methods

The Cancer Genome Atlas and Oncomine portal were used to test the level of PREX1 in gastric cancer tissues. The Kaplan Meier was utilized to evaluate the survival rate in high and low PREX1 expressing patient groups, including the examination of overall survival (OS) and post-progression survival (PPS). The Gene Set Enrichment Analysis was applied to screen the potential PREX1-mediated pathways. The correlation analysis was achieved in the cBioPortal for Cancer Genomics. The mRNA level of PREX1 was examined by reverse transcription quantitative polymerase chain reaction, and the protein level was evaluated by western blotting assay. The dual luciferase reporter assay was applied to test the activation of the TGFβ pathway. The effect of PREX1 in the regulation of metastasis in gastric cancer was assessed by wound healing and Transwell assays.

Research results

PREX1 was highly expressed in gastric cancer tissues, and the expression level of PREX1 was positively correlated with patient stage, tumor grade, and lymph node metastasis. Furthermore, the high PREX1 level patients showed lower survival rate in OS and PPS, and the difference in OS was only discovered in the intestinal-specific gastric cancer patients. PREX1 expression was also closely linked with the cell adhesion and TGF-β related regulators. TGF-β1 could induce PREX1 expression, and PREX1 could activate TGF-β pathway. Overexpression of PREX1 could enhance the migration and invasion activity in vitro.

Research conclusions

PREX1 is overexpressed in gastric cancer tissues and is involved in the development of gastric cancer. PREX1 could serve as a value prognostic biomarker in the prediction of OS and PPS. The mechanism study showed PREX1 is closely involved with the regulation of the cell adhesion process and TGF-β pathway in gastric cancer. PREX1 has a feedback regulation relationship with TGF-β and acts an enhancer in the regulation of metastasis in gastric cancer.

Research perspectives

In this study, we firstly identified that PREX1 was overexpressed in gastric cancer and involved in the development of disease. PREX1 could act as a valuable prognostic marker, and the feedback regulation between PREX1 and TGF-β signaling pathway might contribute to the metastasis of gastric cancer cells. In future work, the detailed regulation between TGF-β and PREX1 should be studied as well as whether PREX1 could directly interact with TGF-β.