Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Surg. Jun 27, 2024; 16(6): 1803-1824
Published online Jun 27, 2024. doi: 10.4240/wjgs.v16.i6.1803
FDX1 as a novel biomarker and treatment target for stomach adenocarcinoma
Xian-Ze Xie, Lei Zuo, Wei Huang, Qiao-Mei Fan, Ya-Yun Weng, Wen-Dong Yao, Jia-Li Jiang, Jia-Qi Jin
Xian-Ze Xie, Wei Huang, Qiao-Mei Fan, Ya-Yun Weng, Wen-Dong Yao, Jia-Li Jiang, Jia-Qi Jin, Department of Pharmacy, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310018, Zhejiang Province, China
Lei Zuo, Anhui Province Huainan City Shou County Agricultural Machinery Affairs Management Center, Huainan 232200, Anhui Province, China.
Co-first authors: Xian-Ze Xie and Lei Zuo.
Author contributions: Xie XZ and Zuo L designed the research; Huang W, Fan QM, Weng YY, Yao WD, Jiang JL and Jin JQ contributed new reagents/analytic tools; Huang W, Fan QM, Weng YY, Yao WD, Jiang JL and Jin JQ analyzed the data; Xie XZ and Zuo L wrote the paper; all authors were involved in the critical review of the results and have contributed to, read, and approved the final manuscript. Xie XZ and Zuo L contributed equally to this work as co-first authors equally to this work. Xie XZ and Zhuo L were named co-first authors on three grounds. First of all, the research is a collaborative effort, which precisely reflects the distribution of responsibilities and ensures efficient communication and post-submission management, thus improving the quality and reliability of the paper. Second, the research team brings together diverse expertise in different fields, a designation that highlights the diversity of the team's characteristics and promotes multiple perspectives for deeper understanding. Third, both authors have made equal contributions in the research process, and this naming principle recognizes their equal contributions while emphasizing the spirit of teamwork.
Supported by The Medical and Health Research Project of Zhejiang Province, No. 2021RC097.
Conflict-of-interest statement: Dr. Jin has nothing to disclose.
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: Jia-Qi Jin, BSc, Pharmacist, Department of Pharmacy, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), No. 9 Road, 9 Dajie, Qiantang District, Hangzhou 310018, Zhejiang Province, China. 13806509322@163.com
Received: March 21, 2024
Revised: April 25, 2024
Accepted: April 28, 2024
Published online: June 27, 2024
Processing time: 100 Days and 17.1 Hours
Abstract
BACKGROUND

Stomach adenocarcinoma (STAD) is one of the main reasons for cancer-related deaths worldwide. This investigation aimed to define the connection between STAD and Cuproptosis-related genes (CRGs). Cuproptosis is a newly identified form of mitochondrial cell death triggered by copper.

AIM

To explore the identification of potential biomarkers for STAD disease based on cuproptosis.

METHODS

A predictive model using Gene Ontology (GO), Least Absolute Shrinkage and Selection Operator (LASSO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Variation Analysis (GSVA), and Gene Set Enrichment Analysis analyzed gene interconnections, focusing on 3 copper-related genes and their expression in The Cancer Genome Atlas-STAD. Networks for mRNA-miRNA and mRNA-transcription factor interactions were constructed. The prognostic significance of CRG scores was evaluated using time-receiver operating characteristic, Kaplan-Meier curves, and COX regression analysis. Validation was conducted with datasets GSE26942, GSE54129, and GSE66229. Expression of copper-related differentially expressed genes was also analyzed in various human tissues and gastric cancer subpopulations using the human protein atlas.

RESULTS

Three significant genes (FDX1, LIAS, MTF1) were identified and selected via LASSO analysis to predict and classify individuals with STAD into high and low CRG score subgroups. These genes were down-regulated in both risk categories. GO and KEGG analyses highlighted their involvement mainly in the electron transport chain. After validating their differential expression, FDX1 emerged as the most accurate diagnostic marker for gastric cancer. Additionally, the RCircos package localized FDX1 on chromosome 11.

CONCLUSION

Our study revealed that FDX1 could be a potential biomarker and treatment target for gastric malignancy, providing new ideas for further scientific research.

Keywords: Stomach adenocarcinoma disease; Copper death; FDX1; prognostic biomarkers; Cuproptosis-related genes

Core Tip: This study explores the novel link between cuproptosis-related genes (CRGs) and stomach adenocarcinoma (STAD), identifying FDX1 as a potential biomarker and therapeutic target. Utilizing comprehensive analyses, including Gene Set Enrichment Analysis and Least Absolute Shrinkage and Selection Operator regression, we categorized STAD patients into high and low risk based on CRG scores. FDX1, along with two other genes, demonstrated significant diagnostic and prognostic potential, suggesting a new avenue for targeted therapies in gastric cancer treatment.