通过生物信息学分析识别和验证与心肌纤维化相关的潜在标记物

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Genetics Pub Date : 2024-10-10 DOI:10.1007/s10528-024-10937-9
Jiazhuo Huang, Zhentao Shi, Zhifeng Huang, Shaobin Lai
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引用次数: 0

摘要

越来越多的证据表明,心肌纤维化(MF)经常与免疫和代谢紊乱交织在一起。本综述旨在深入探讨免疫相关特征基因在心肌纤维化发病和进展过程中的关键作用。这一探索具有重要意义,因为了解 MF 的内在机制对于开发有效的诊断和治疗策略至关重要。我们从 GEO 数据库下载了有关心肌纤维化和非纤维化的数据集 GSE9735。利用 R 软件中的 "limma "软件包识别差异表达基因(DEGs)。然后,通过基因本体(GO)和京都基因组百科全书(KEGG)通路富集分析确定 DEG 的生物学功能。XCell用于估计基质和免疫细胞的组成模式。基于STRING分析软件构建了蛋白质-蛋白质相互作用(PPI)网络,并筛选了枢纽基因和分析了功能模块。分析了枢纽基因与免疫细胞亚型的相关性。相关系数大于 0.45 且 p-value
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Identification and Verification of Potential Markers Related to Myocardial Fibrosis by Bioinformatics Analysis.

Mounting evidence indicates that myocardial fibrosis (MF) is frequently intertwined with immune and metabolic disorders. This comprehensive review aims to delve deeply into the crucial role of immune-related signature genes in the pathogenesis and progression of MF. This exploration holds significant importance as understanding the underlying mechanisms of MF is essential for developing effective diagnostic and therapeutic strategies. The dataset GSE9735 about myocardial fibrosis and non-fibrosis was downloaded from GEO database. Differentially expressed genes (DEGs) were identified by 'limma' package in R software. Then, the biological function of DEG was determined by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. XCell was used to estimate the composition pattern of matrix and immune cells. Protein-protein interaction (PPI) network was constructed based on STRING analysis software, and Hub genes were screened and functional modules were analyzed. The correlation between hub genes and immune cell subtypes was analyzed. Hub genes with |correlation coefficient|> 0.45 and p-value < 0.05 were used as characteristic biomarkers. Finally, the logistic regression model is used to verify the three markers in the training set and verification set (GSE97358 and GSE225336). A total of 635 DEGs were identified. Functional enrichment analysis shows that inflammation and immune response, extracellular matrix and structural remodeling play an important role in the pathological mechanism of MF. Immune cell infiltration analysis showed that immune cells (Plasma cells, Eosinophils, Chondrocytes and Th2 cells) significantly changed in MF pathological conditions. In PPI network analysis, IL1β, TTN, PTPRC, IGF1, ALDH1A1, CYP26A1, ALDH1A3, MYH11, CSF1R and CD80 were identified as hub genes, among which IL1β, CYP26A1 and GNG2 were regarded as immune-related characteristic markers. The AUC scores of the three biomarkers are all above 0.65, which proves that they have a good discrimination effect in MF. In this study, three immune-related genes were identified as diagnostic biomarkers of MF, which provided a new perspective for exploring the molecular mechanism of MF. This study takes a comprehensive approach to understanding the intricate relationship between myocardial fibrosis and immune metabolism. By identifying key immune-related biomarkers, this study not only reveals the molecular basis of myocardial fibrosis but also paves the way for the development of novel diagnostic tools and therapeutic strategies. These findings are critical for improving patient prognosis and may have broader implications for studying and treating other cardiovascular diseases associated with immune dysregulation.

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来源期刊
Biochemical Genetics
Biochemical Genetics 生物-生化与分子生物学
CiteScore
3.90
自引率
0.00%
发文量
133
审稿时长
4.8 months
期刊介绍: Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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