Development of oxidative stress- and ferroptosis-related prognostic signature in gastric cancer and identification of CDH19 as a novel biomarker.

IF 3.8 3区 医学 Q2 GENETICS & HEREDITY Human Genomics Pub Date : 2024-11-05 DOI:10.1186/s40246-024-00682-w
Shibo Wang, Siyi Zhang, Xiaoxuan Li, Chuanyu Leng, Xiangxue Li, Jing Lv, Shufen Zhao, Wensheng Qiu, Jing Guo
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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.

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开发胃癌氧化应激和铁蛋白沉积相关预后特征并确定 CDH19 为新型生物标记物
背景:铁变性是一种独特的细胞死亡模式,它依赖于铁,并与氧化应激和脂质过氧化有关。氧化应激和铁氧化是导致细胞代谢异常的重要机制,一直是癌症研究的热门领域:方法:最初,通过交叉氧化应激和铁变态反应的基因集,获得了 76 个氧化应激和铁变态反应相关基因(OFRGs)。随后,利用 PPI 网络筛选出最佳 OFRGs,并将个体分为两个 OFRG 亚型(K = 2)。随后,我们成功构建并验证了由 SLC7A2、Cadherin 19 (CDH19) 和 CCN1 组成的预后特征。为了进一步发现胃癌(GC)的潜在生物标志物,我们检测了CDH19的表达水平,研究了敲除CDH19对GC细胞生物学行为的影响,并探讨了CDH19是否参与了铁变态反应和氧化应激过程:结果:研究结果显示,低危评分组患者的免疫抑制细胞浸润较少,免疫逃逸和免疫功能失调的发生率较低,化疗和免疫治疗的疗效较好,生存预后较好。qRT-PCR检测表明,CDH19在GC细胞中的表达量明显较高。通过实验,我们证明了敲除 CDH19 可影响 ACSL4 和 GPX4 的转录水平,增加细胞内铁离子浓度和活性氧(ROS)的积累,抑制 GC 细胞的增殖和迁移:我们建立了一个与 OFRG 相关的特征来预测 GC 患者的预后和治疗反应性,并确定 CDH19 为 GC 的可能治疗靶点。
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来源期刊
Human Genomics
Human Genomics GENETICS & HEREDITY-
CiteScore
6.00
自引率
2.20%
发文量
55
审稿时长
11 weeks
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.
期刊最新文献
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