{"title":"Development of oxidative stress- and ferroptosis-related prognostic signature in gastric cancer and identification of CDH19 as a novel biomarker.","authors":"Shibo Wang, Siyi Zhang, Xiaoxuan Li, Chuanyu Leng, Xiangxue Li, Jing Lv, Shufen Zhao, Wensheng Qiu, Jing Guo","doi":"10.1186/s40246-024-00682-w","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis is a unique mode of cell death that is iron-dependent and associated with oxidative stress and lipid peroxidation. Oxidative stress and ferroptosis are essential mechanisms leading to metabolic abnormalities in cells and have been popular areas in cancer research.</p><p><strong>Methods: </strong>Initially, 76 oxidative stress and ferroptosis-related genes (OFRGs) were acquired by intersecting the gene sets from oxidative stress and ferroptosis. Afterwards, optimal OFRGs were screened using PPI networks, and individuals were separated into two OFRG subtypes (K = 2). Subsequently, we successfully constructed and verified a prognostic signature comprising SLC7A2, Cadherin 19 (CDH19), and CCN1. To further uncover potential biomarkers of gastric cancer (GC), we examined the expression level of CDH19, investigated the effects of knocking down CDH19 on the biological behavior of GC cells, and explored whether CDH19 is involved in ferroptosis and oxidative stress processes.</p><p><strong>Results: </strong>According to the findings, individuals in the low-risk scoring group have less infiltration of immune suppressive cells, fewer occurrences of immune escape and dysfunction, greater efficacy in chemotherapy and immunotherapy, and better survival outcomes. The qRT-PCR assay indicated that CDH19 expression was significantly higher in GC cells. Through experiments, we demonstrated that knocking down CDH19 can affect the transcription levels of ACSL4 and GPX4, increase intracellular iron ion concentration and accumulation of reactive oxygen species (ROS), and inhibit the proliferation and migration of GC cells.</p><p><strong>Conclusion: </strong>We developed an OFRG-related signature to predict the prognosis and treatment responsiveness of individuals with GC and identified CDH19 as a possible therapeutic target for GC.</p>","PeriodicalId":13183,"journal":{"name":"Human Genomics","volume":null,"pages":null},"PeriodicalIF":3.8000,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536560/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Genomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40246-024-00682-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Ferroptosis is a unique mode of cell death that is iron-dependent and associated with oxidative stress and lipid peroxidation. Oxidative stress and ferroptosis are essential mechanisms leading to metabolic abnormalities in cells and have been popular areas in cancer research.
Methods: Initially, 76 oxidative stress and ferroptosis-related genes (OFRGs) were acquired by intersecting the gene sets from oxidative stress and ferroptosis. Afterwards, optimal OFRGs were screened using PPI networks, and individuals were separated into two OFRG subtypes (K = 2). Subsequently, we successfully constructed and verified a prognostic signature comprising SLC7A2, Cadherin 19 (CDH19), and CCN1. To further uncover potential biomarkers of gastric cancer (GC), we examined the expression level of CDH19, investigated the effects of knocking down CDH19 on the biological behavior of GC cells, and explored whether CDH19 is involved in ferroptosis and oxidative stress processes.
Results: According to the findings, individuals in the low-risk scoring group have less infiltration of immune suppressive cells, fewer occurrences of immune escape and dysfunction, greater efficacy in chemotherapy and immunotherapy, and better survival outcomes. The qRT-PCR assay indicated that CDH19 expression was significantly higher in GC cells. Through experiments, we demonstrated that knocking down CDH19 can affect the transcription levels of ACSL4 and GPX4, increase intracellular iron ion concentration and accumulation of reactive oxygen species (ROS), and inhibit the proliferation and migration of GC cells.
Conclusion: We developed an OFRG-related signature to predict the prognosis and treatment responsiveness of individuals with GC and identified CDH19 as a possible therapeutic target for GC.
期刊介绍:
Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics.
Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.