Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2024; 16(5): 2018-2037
Published online May 15, 2024. doi: 10.4251/wjgo.v16.i5.2018
Predictive model using four ferroptosis-related genes accurately predicts gastric cancer prognosis
Li Wang, Wei-Hua Gong
Li Wang, Department of Emergency, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Wei-Hua Gong, Department of Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang Province, China
Author contributions: Wang L contributed data compilation, formal analysis, writing-original version; Gong WH contributed methodology, writing original draft. conceptualization, obtaining funding, mentoring, writing-review and editing.
Institutional review board statement: The protocol of the study was reviewed and approved by the Ethics Committee of the Second Affiliated Hospital Zhejiang University School of Medicine (2023-0177).
Institutional animal care and use committee statement: This study and included experimental procedures were approved by the institutional animal care and use committee of Zhejiang Chinese Medicine University (No. IACUC-20230410-21). All animal housing and experiments were conducted in strict accordance with the institutional guidelines for care and use of laboratory animals.
Informed consent statement: All participants signed informed consent forms.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data analyzed in this study are available in the cancer genome atlas database (https://portal.gdc.cancer.gov/); FerrDb Database (http://www.zhounan.org/ferrdb/current/). And the GSE datas downland from below address: (GSE99553: https://www.ncbi.nlm.nih.gov/geo/geo2r/?acc=GSE99553), (GSE84426: https://www.ncbi.nlm.nih.gov/geo/geo2r/?acc=GSE84426). And the experimental data supporting the findings of this study are available within the article. The Supplementary Dataset File was the WB result of Fig 7C and Fig 8E.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei-Hua Gong, PhD, Researcher, Department of Surgery, The Second Affiliated Hospital Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310052, Zhejiang Province, China. weihuagong@zju.edu.cn
Received: October 21, 2023
Peer-review started: October 21, 2023
First decision: January 25, 2024
Revised: January 31, 2024
Accepted: March 8, 2024
Article in press: March 8, 2024
Published online: May 15, 2024
Processing time: 201 Days and 12.2 Hours
ARTICLE HIGHLIGHTS
Research background

Gastric cancer (GC) is a common malignancy of the digestive system. Ferroptosis or iron-dependent programmed cell death, has been linked to GC, although there has been little research on the link between Helicobacter pylori (H. pylori) infection-related GC and ferroptosis.

Research motivation

This study investigated the coregulated differentially expressed genes (co-DEGs) among ferroptosis-related genes (FRGs) in H. pylori infection-related GCs and investigated the relationship between the expression of these co-DEGs and clinical prognosis.

Research objectives

This study developed a prognostic model for GC based on co-DEGs among FRGs. Gene expression profiles from GC patients and H. pylori-associated GC patients were analyzed.

Research methods

Gene expression profiles of GC patients and those with H. pylori-associated GC were obtained from the cancer genome atlas and gene expression omnibus (GEO) databases. The FRGs were acquired from the FerrDb database. A ferroptosis-related gene prognostic index (FRGPI) was created using least absolute shrinkage and selection operator–Cox regression. The predictive ability of the FRGPI was validated in the GEO cohort. Finally, we verified the expression of the hub genes and the activity of the ferroptosis inducer FIN56 in GC cell lines and tissues.

Research results

The four hub genes (NOX4, MTCH1, GABARAPL2, and SLC2A3) accurately predicted GC and H. pylori-associated GC. The FRGPI based on the hub genes independently predicted patient survival. High-risk GC patients had notably worse overall survival. The FRGPI was found to be a significant predictor of GC prognosis and correlated with disease progression. The expression of immune checkpoint proteins increased in the high-risk group. Hub genes were highly overexpressed in GC cell lines and tissues, primarily at the cell membrane. The ferroptosis inducer FIN56 inhibited GC cell proliferation in a dose-dependent manner.

Research conclusions

The predictive model provides an accurate prognosis for GC patients and helps evaluate immunotherapy efficacy.

Research perspectives

The mechanism of the hub gene in the occurrence and development of GC was studied, and its effect on iron death in GC cells was analyzed.