Hub genes, a diagnostic model, and immune infiltration based on ferroptosis-linked genes in schizophrenia

IF 2 Q3 NEUROSCIENCES
Kun Lian , Yongmei Li , Wei Yang , Jing Ye , Hongbing Liu , Tianlan Wang , Guangya Yang , Yuqi Cheng , Xiufeng Xu
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引用次数: 0

Abstract

Background

Schizophrenia (SCZ) is a prevalent and serious mental disorder, and the exact pathophysiology of this condition is not fully understood. In previous studies, it has been proven that ferroprotein levels are high in SCZ. It has also been shown that this inflammatory response may modify fibromodulin. Accumulating evidence indicates a strong link between metabolism and ferroptosis. Therefore, the present study aims to identify ferroptosis‐linked hub genes to further investigate the role that ferroptosis plays in the development of SCZ.

Material and methods

From the GEO database, four microarray data sets on SCZ (GSE53987, GSE38481, GSE18312, and GSE38484) and ferroptosis‐linked genes were extracted. Using the prefrontal cortex expression matrix of SCZ patients and healthy individuals as the control group from GSE53987, weighted gene co‐expression network analysis (WGCNA) was performed to discover SCZ‐linked module genes. From the feed, genes associated with ferroptosis were retrieved. The intersection of the module and ferroptosis-linked genes was done to obtain the hub genes. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and Gene Set Enrichment Analysis (GSEA) were conducted. The SCZ diagnostic model was established using logistic regression, and the GSE38481, GSE18312, and GSE38484 data sets were used to validate the model. Finally, hub genes linked to immune infiltration were examined.

Results

A total of 13 SCZ module genes and 7 hub genes linked to ferroptosis were obtained: DECR1, GJA1, EFN2L2, PSAT1, SLC7A11, SOX2, and YAP1. The GO/KEGG/GSEA study indicated that these hub genes were predominantly enriched in mitochondria and lipid metabolism, oxidative stress, immunological inflammation, ferroptosis, Hippo signaling pathway, AMP‐activated protein kinase pathway, and other associated biological processes. The diagnostic model created using these hub genes was further confirmed using the data sets of three blood samples from patients with SCZ. The immune infiltration data showed that immune cell dysfunction enhanced ferroptosis and triggered SCZ.

Conclusion

In this study, seven critical genes that are strongly associated with ferroptosis in patients with SCZ were discovered, a valid clinical diagnostic model was built, and a novel therapeutic target for the treatment of SCZ was identified by the investigation of immune infiltration.

精神分裂症中的枢纽基因、诊断模型和基于铁蛋白沉积相关基因的免疫浸润
背景精神分裂症(SCZ)是一种普遍存在的严重精神障碍,其确切的病理生理学尚不完全清楚。以往的研究证明,精神分裂症患者体内的铁蛋白水平较高。研究还表明,这种炎症反应可能会改变纤维蛋白。越来越多的证据表明,新陈代谢与铁蛋白沉积之间存在密切联系。材料与方法从 GEO 数据库中提取了 SCZ 的四个微阵列数据集(GSE53987、GSE38481、GSE18312 和 GSE38484)以及与铁变态反应相关的基因。利用 GSE53987 中 SCZ 患者和健康人作为对照组的前额叶皮层表达矩阵,进行加权基因共表达网络分析(WGCNA),以发现与 SCZ 相关的模块基因。从中检索出了与铁中毒相关的基因。模块基因与铁变态反应相关基因的交集被用于获得枢纽基因。然后进行了基因本体(GO)、京都基因组百科全书(KEGG)通路富集分析和基因组富集分析(GSEA)。利用逻辑回归建立了 SCZ 诊断模型,并利用 GSE38481、GSE18312 和 GSE38484 数据集验证了该模型。结果共获得了 13 个 SCZ 模块基因和 7 个与铁变态反应相关的枢纽基因:结果共获得 13 个 SCZ 模块基因和 7 个与铁突变相关的枢纽基因:DECR1、GJA1、EFN2L2、PSAT1、SLC7A11、SOX2 和 YAP1。GO/KEGG/GSEA 研究表明,这些枢纽基因主要富集在线粒体和脂质代谢、氧化应激、免疫炎症、铁变态反应、Hippo 信号通路、AMP 激活蛋白激酶通路以及其他相关的生物过程中。利用这些枢纽基因创建的诊断模型通过 SCZ 患者的三个血液样本数据集得到了进一步证实。免疫浸润数据显示,免疫细胞功能障碍会增强铁蛋白沉积并诱发SCZ。结论本研究发现了与SCZ患者铁蛋白沉积密切相关的7个关键基因,建立了有效的临床诊断模型,并通过免疫浸润的研究发现了治疗SCZ的新靶点。
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来源期刊
IBRO Neuroscience Reports
IBRO Neuroscience Reports Neuroscience-Neuroscience (all)
CiteScore
2.80
自引率
0.00%
发文量
99
审稿时长
14 weeks
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