Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2023; 15(7): 1200-1214
Published online Jul 15, 2023. doi: 10.4251/wjgo.v15.i7.1200
Clinical significance and potential application of cuproptosis-related genes in gastric cancer
Jia-Ning Yan, Li-Hua Guo, Dan-Ping Zhu, Guo-Liang Ye, Yong-Fu Shao, Han-Xuan Zhou
Jia-Ning Yan, Li-Hua Guo, Dan-Ping Zhu, Guo-Liang Ye, Yong-Fu Shao, Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315000, Zhejiang Province, China
Han-Xuan Zhou, Department of Pharmacy, Yinzhou Integrated TCM and Western Medicine Hospital, Ningbo 315000, Zhejiang Province, China
Author contributions: Yan JN designed and performed the research and wrote the paper; Shao YF and Ye GL designed the research and supervised the report; Zhou HX and Guo LH designed the research and contributed to the analysis; Shao YF and Zhu DP were responsible for the revision of the manuscript for important intellectual content; All authors expressed approval of the final version to be submitted.
Supported by The Key Scientific and Technological Projects of Ningbo, No. 2021Z133.
Institutional review board statement: Our research is based on the Cancer Genome Atlas (TCGA, https://tega-data.nci.nih.gov/) database, the Genotype-Tissue Expression (GTEx) data portal (https://www.gtexportal.org/home/index.html) and the Gene Expression Omnibus (GEO, https://www.nebi.nlm.nih.gov/gds) database. All of these are open-access public databases. Thus, no institutional review board approval was required.
Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article.
Data sharing statement: The technical appendix, statistical code, and datasets are available from the corresponding author at fyshaoyongfu@nbu.edu.cn.
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: Yong-Fu Shao, MD, PhD, Doctor, Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, No. 247 Renmin Road, Ningbo 315000, Zhejiang Province, China. fyshaoyongfu@nbu.edu.cn
Received: February 4, 2023
Peer-review started: February 4, 2023
First decision: March 21, 2023
Revised: March 28, 2023
Accepted: May 6, 2023
Article in press: May 6, 2023
Published online: July 15, 2023
Abstract
BACKGROUND

Worldwide, gastric cancer (GC) is a common lethal solid malignancy with a poor prognosis. Cuproptosis is a novel type of cell death mediated by protein lipoylation and may be related to GC prognosis.

AIM

To offer new insights to predict GC prognosis and provide multiple therapeutic targets related to cuproptosis-related genes (CRGs) for future therapy.

METHODS

We collected data from several public data portals, systematically estimated the expression level and prognostic values of CRGs in GC samples, and investigated related mechanisms using public databases and bioinformatics.

RESULTS

Our results revealed that FDX1, LIAS, and MTF1 were differentially expressed in GC samples and exhibited important prognostic significance in The Cancer Genome Atlas (TCGA) cohort. We constructed a nomogram model for overall survival and disease-specific survival prediction and validated it via calibration plots. Mecha-nistically, immune cell infiltration and DNA methylation prominently affected the survival time of GC patients. Moreover, protein-protein interaction network, KEGG pathway and gene ontology enrichment analyses demonstrated that FDX1, LIAS, MTF1 and related proteins play key roles in the tricarboxylic acid cycle and cuproptosis. Gene Expression Omnibus database validation showed that the expression levels of FDX1, LIAS, and MTF1 were consistent with those in the TCGA cohort. Top 10 perturbagens has been filtered by Connectivity Map.

CONCLUSION

In conclusion, FDX1, LIAS, and MTF1 could serve as potential prognostic biomarkers for GC patients and provide novel targets for immunotarget therapy.

Keywords: Cuproptosis, Prognosis, Gastric cancer, Biomarker, Nomogram, Bioinformatics

Core Tip: In this study, the molecular biological mechanisms of cuproptosis-related genes (CRGs) were explored in gastric cancer, and clinical prognostic models for gastric cancer treatment were constructed by interactively analysing the links among CRGs and clinical information using bioinformatics. We constructed a significant prognostic nomogram model for gastric cancer and found that FDX1, LIAS, and MTF1 could serve as potential prognostic biomarkers for gastric cancer patients and provide novel targets for immunotarget therapy.