胃腺癌（STAD）是全世界癌症相关死亡的主要原因之一。本研究旨在明确 STAD 和铜中毒相关基因 (CRG) 之间的联系。铜中毒是一种新发现的由铜引发的线粒体细胞死亡形式。基于铜中毒探索 STAD 疾病潜在生物标志物的鉴定。使用基因本体论 (GO)、最小绝对收缩和选择算子 (LASSO)、京都百科全书的预测模型基因和基因组分析 (KEGG)、基因集变异分析 (GSVA) 和基因集富集分析分析了基因互连，重点关注癌症基因组图谱-STAD 中的 3 个铜相关基因及其表达。构建了 mRNA-miRNA 和 mRNA-转录因子相互作用的网络。使用时间接收器操作特征、Kaplan-Meier 曲线和 COX 回归分析评估 CRG 评分的预后意义。使用数据集 GSE26942、GSE54129 和 GSE66229 进行验证。还利用人类蛋白图谱分析了不同人体组织和胃癌亚群中与铜相关的差异表达基因的表达。通过LASSO分析鉴定和选择了三个显着基因（FDX1、LIAS、MTF1）来预测STAD个体并将其分类为高和低 CRG 分数亚组。这些基因在两个风险类别中均被下调。 GO 和 KEGG 分析强调了它们主要参与电子传输链。在验证其差异表达后，FDX1 成为胃癌最准确的诊断标志物。此外，RCircos包将FDX1定位在11号染色体上。我们的研究表明，FDX1可能成为胃恶性肿瘤的潜在生物标志物和治疗靶点，为进一步的科学研究提供了新思路。©作者2024。百世登出版集团公司出版。 版权所有。

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.©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.