Hongjiao Zhang, Jinbo Zhan, Juanjuan Zhou, Liping Liu, Yan He, Yi Le, Weiqi Liu, Ling Zhou, Yawen Liu, Xiaojun Xiang
{"title":"基于新型吸铁相关预后模型和体外实验的HCAR1作为胃癌吸铁相关生物标志物的鉴定","authors":"Hongjiao Zhang, Jinbo Zhan, Juanjuan Zhou, Liping Liu, Yan He, Yi Le, Weiqi Liu, Ling Zhou, Yawen Liu, Xiaojun Xiang","doi":"10.1093/carcin/bgaf030","DOIUrl":null,"url":null,"abstract":"<p><p>Currently, research on ferroptosis-related prognostic models for gastric cancer is limited, whereas traditional predictive models often have a narrow perspective and low accuracy. In this study, we systematically analyzed the expression patterns of ferroptosis-related genes in patients with gastric adenocarcinoma and evaluated their prognostic value. Using data from The Cancer Genome Atlas (TCGA) and the FerrDb database, we developed a ferroptosis-related prognostic risk model based on four genes: hydroxycarboxylic acid receptor 1 (HCAR1), branched-chain amino acid transaminase 1 (BCAT1), ceruloplasmin (CP), and dickkopf-1 (DKK1). This model demonstrated strong prognostic value and potential clinical relevance in stratifying gastric cancer patients by overall survival outcomes. ferroptosis-related prognostic risk model. Compared to traditional clinicopathological features, the risk score derived from this model exhibited superior predictive accuracy for overall survival in patients with gastric cancer and served as an independent prognostic factor. Functional enrichment analysis revealed that the risk score was primarily enriched for extracellular matrix-related pathways. Additionally, the risk score was significantly correlated with TME signature genes, immune checkpoint expression, and immune cell infiltration in stomach adenocarcinoma (STAD). Mechanistic studies revealed that HCAR1 is abnormally overexpressed in gastric cancer tissues and is associated with a poor prognosis. It exerted its effects by regulating the GPX4/SLC7A11 axis to inhibit lipid peroxidation and malondialdehyde accumulation, thereby obstructing ferroptosis. Experimental validation demonstrated that the downregulation of HCAR1 promoted ferroptosis and suppressed malignant tumor phenotypes, suggesting that both the gene and its associated risk model hold significant clinical value as potential therapeutic targets and prognostic biomarkers.</p>","PeriodicalId":9446,"journal":{"name":"Carcinogenesis","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Identification of HCAR1 as a ferroptosis-related biomarker of gastric cancer based on a novel ferroptosis-related prognostic model and in vitro experiments.\",\"authors\":\"Hongjiao Zhang, Jinbo Zhan, Juanjuan Zhou, Liping Liu, Yan He, Yi Le, Weiqi Liu, Ling Zhou, Yawen Liu, Xiaojun Xiang\",\"doi\":\"10.1093/carcin/bgaf030\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Currently, research on ferroptosis-related prognostic models for gastric cancer is limited, whereas traditional predictive models often have a narrow perspective and low accuracy. In this study, we systematically analyzed the expression patterns of ferroptosis-related genes in patients with gastric adenocarcinoma and evaluated their prognostic value. Using data from The Cancer Genome Atlas (TCGA) and the FerrDb database, we developed a ferroptosis-related prognostic risk model based on four genes: hydroxycarboxylic acid receptor 1 (HCAR1), branched-chain amino acid transaminase 1 (BCAT1), ceruloplasmin (CP), and dickkopf-1 (DKK1). This model demonstrated strong prognostic value and potential clinical relevance in stratifying gastric cancer patients by overall survival outcomes. ferroptosis-related prognostic risk model. Compared to traditional clinicopathological features, the risk score derived from this model exhibited superior predictive accuracy for overall survival in patients with gastric cancer and served as an independent prognostic factor. Functional enrichment analysis revealed that the risk score was primarily enriched for extracellular matrix-related pathways. Additionally, the risk score was significantly correlated with TME signature genes, immune checkpoint expression, and immune cell infiltration in stomach adenocarcinoma (STAD). Mechanistic studies revealed that HCAR1 is abnormally overexpressed in gastric cancer tissues and is associated with a poor prognosis. It exerted its effects by regulating the GPX4/SLC7A11 axis to inhibit lipid peroxidation and malondialdehyde accumulation, thereby obstructing ferroptosis. Experimental validation demonstrated that the downregulation of HCAR1 promoted ferroptosis and suppressed malignant tumor phenotypes, suggesting that both the gene and its associated risk model hold significant clinical value as potential therapeutic targets and prognostic biomarkers.</p>\",\"PeriodicalId\":9446,\"journal\":{\"name\":\"Carcinogenesis\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-06-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Carcinogenesis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/carcin/bgaf030\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Carcinogenesis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/carcin/bgaf030","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Identification of HCAR1 as a ferroptosis-related biomarker of gastric cancer based on a novel ferroptosis-related prognostic model and in vitro experiments.
Currently, research on ferroptosis-related prognostic models for gastric cancer is limited, whereas traditional predictive models often have a narrow perspective and low accuracy. In this study, we systematically analyzed the expression patterns of ferroptosis-related genes in patients with gastric adenocarcinoma and evaluated their prognostic value. Using data from The Cancer Genome Atlas (TCGA) and the FerrDb database, we developed a ferroptosis-related prognostic risk model based on four genes: hydroxycarboxylic acid receptor 1 (HCAR1), branched-chain amino acid transaminase 1 (BCAT1), ceruloplasmin (CP), and dickkopf-1 (DKK1). This model demonstrated strong prognostic value and potential clinical relevance in stratifying gastric cancer patients by overall survival outcomes. ferroptosis-related prognostic risk model. Compared to traditional clinicopathological features, the risk score derived from this model exhibited superior predictive accuracy for overall survival in patients with gastric cancer and served as an independent prognostic factor. Functional enrichment analysis revealed that the risk score was primarily enriched for extracellular matrix-related pathways. Additionally, the risk score was significantly correlated with TME signature genes, immune checkpoint expression, and immune cell infiltration in stomach adenocarcinoma (STAD). Mechanistic studies revealed that HCAR1 is abnormally overexpressed in gastric cancer tissues and is associated with a poor prognosis. It exerted its effects by regulating the GPX4/SLC7A11 axis to inhibit lipid peroxidation and malondialdehyde accumulation, thereby obstructing ferroptosis. Experimental validation demonstrated that the downregulation of HCAR1 promoted ferroptosis and suppressed malignant tumor phenotypes, suggesting that both the gene and its associated risk model hold significant clinical value as potential therapeutic targets and prognostic biomarkers.
期刊介绍：
Carcinogenesis: Integrative Cancer Research is a multi-disciplinary journal that brings together all the varied aspects of research that will ultimately lead to the prevention of cancer in man. The journal publishes papers that warrant prompt publication in the areas of Biology, Genetics and Epigenetics (including the processes of promotion, progression, signal transduction, apoptosis, genomic instability, growth factors, cell and molecular biology, mutation, DNA repair, genetics, etc.), Cancer Biomarkers and Molecular Epidemiology (including genetic predisposition to cancer, and epidemiology), Inflammation, Microenvironment and Prevention (including molecular dosimetry, chemoprevention, nutrition and cancer, etc.), and Carcinogenesis (including oncogenes and tumor suppressor genes in carcinogenesis, therapy resistance of solid tumors, cancer mouse models, apoptosis and senescence, novel therapeutic targets and cancer drugs).
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