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...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 differ-entially 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.展开更多
铜离子导致细胞死亡是一种铜依赖性且独特的细胞死亡,与其他现有的形式的细胞死亡不同。长期以来,铜诱导的细胞死亡是否可以导致细胞死亡及其导致细胞死亡的机制一直存在争议,直到最近的研究铜死亡cuproptosis的机制被发现。在那之后,...铜离子导致细胞死亡是一种铜依赖性且独特的细胞死亡,与其他现有的形式的细胞死亡不同。长期以来,铜诱导的细胞死亡是否可以导致细胞死亡及其导致细胞死亡的机制一直存在争议,直到最近的研究铜死亡cuproptosis的机制被发现。在那之后,越来越多的研究人员试图确定cuproptosis与癌症过程之间的关系。因此,在这篇综述中,我们系统地详细介绍了铜离子在人类的全身和细胞代谢过程,以及铜离子在肿瘤中的作用。其次,讲明了cuproptosis的发现过程及其机制,还概述了cuproptosis及其关键基因FDX1与癌症之间的关联,及FDX1与现有的肿瘤药物相互作用的新进展。Cell death caused by copper ions is a copper-dependent and unique cell death that is different from other existing forms of cell death. For a long time, whether copper-induced cell death can lead to cell death and the mechanism by which it leads to cell death have been controversial until recent studies have discovered the mechanism of copper death cuproptosis. Since then, more and more researchers have tried to determine the relationship between cuproptosis and cancer processes. Therefore, in this review, we systematically and in detail introduce the systemic and cellular metabolic processes of copper ions in humans, as well as the role of copper ions in tumors. Secondly, the discovery process and mechanism of cuproptosis are explained, and the association between cuproptosis and its key gene FDX1 and cancer is also outlined, as well as new progress in the interaction between FDX1 and existing tumor drugs.展开更多
基金Supported by The Medical and Health Research Project of Zhejiang Province,No.2021RC097.
文摘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 differ-entially 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.
文摘铜离子导致细胞死亡是一种铜依赖性且独特的细胞死亡,与其他现有的形式的细胞死亡不同。长期以来,铜诱导的细胞死亡是否可以导致细胞死亡及其导致细胞死亡的机制一直存在争议,直到最近的研究铜死亡cuproptosis的机制被发现。在那之后,越来越多的研究人员试图确定cuproptosis与癌症过程之间的关系。因此,在这篇综述中,我们系统地详细介绍了铜离子在人类的全身和细胞代谢过程,以及铜离子在肿瘤中的作用。其次,讲明了cuproptosis的发现过程及其机制,还概述了cuproptosis及其关键基因FDX1与癌症之间的关联,及FDX1与现有的肿瘤药物相互作用的新进展。Cell death caused by copper ions is a copper-dependent and unique cell death that is different from other existing forms of cell death. For a long time, whether copper-induced cell death can lead to cell death and the mechanism by which it leads to cell death have been controversial until recent studies have discovered the mechanism of copper death cuproptosis. Since then, more and more researchers have tried to determine the relationship between cuproptosis and cancer processes. Therefore, in this review, we systematically and in detail introduce the systemic and cellular metabolic processes of copper ions in humans, as well as the role of copper ions in tumors. Secondly, the discovery process and mechanism of cuproptosis are explained, and the association between cuproptosis and its key gene FDX1 and cancer is also outlined, as well as new progress in the interaction between FDX1 and existing tumor drugs.
