Published online Jun 27, 2024. doi: 10.4240/wjgs.v16.i6.1803
Revised: April 25, 2024
Accepted: April 28, 2024
Published online: June 27, 2024
Processing time: 100 Days and 13.7 Hours
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.
To explore the identification of potential biomarkers for STAD disease based on cuproptosis.
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.
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.
Our study revealed that FDX1 could be a potential biomarker and treatment target for gastric malignancy, providing new ideas for further scientific research.
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.