基于炎症和热缩相关基因的肌肉减少症预测模型。

IF 2.8 3区 生物学 Q2 GENETICS & HEREDITY Frontiers in Genetics Pub Date : 2024-12-24 eCollection Date: 2024-01-01 DOI:10.3389/fgene.2024.1491577
Xiaoqing Li, Cheng Wu, Xiang Lu, Li Wang
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引用次数: 0

摘要

背景:肌肉减少症是一种与衰老相关的普遍疾病。炎症和焦亡是引起肌肉减少症的重要原因。方法:从Gene Expression Omnibus (GEO)中获取两个骨骼肌减少症相关数据集(GSE111016和GSE167186),合并后进行批量效应去除。利用“limma”R包鉴定差异表达基因(DEGs)。随后,我们对炎症和热噬相关基因(IPRGs)进行LASSO分析,鉴定出6个hub IPRGs。建立了一种新的骨骼肌衰老模型,并使用独立数据集进行了验证。此外,对DEGs进行了基因本体(GO)富集分析,以及京都基因与基因组百科全书(KEGG)途径分析和基因集富集分析(GSEA)。ssGSEA被用来评估老年人和年轻人健康肌肉群之间免疫细胞比例的差异。通过qRT-PCR方法定量检测6个核心IPRGs的表达水平。结果:共对44例老年样本和68例年轻健康样本进行了DEGs分析。与年轻健康肌肉组织相比,老年肌肉组织中T细胞浸润水平明显降低,肥大细胞和单核细胞浸润水平相对升高。基于6种IPRGs的肌少症诊断筛选模型预测效率高(AUC = 0.871)。qRT-PCR结果表明,这6个IPRGs的表达趋势与数据库中观察到的一致。结论:6个生物标志物- btg2、FOXO3、AQP9、GPC3、CYCS和scn1b -与一个诊断模型一起被鉴定出来,为肌少症的早期诊断提供了一种新的方法。
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Predictive models of sarcopenia based on inflammation and pyroptosis-related genes.

Background: Sarcopenia is a prevalent condition associated with aging. Inflammation and pyroptosis significantly contribute to sarcopenia.

Methods: Two sarcopenia-related datasets (GSE111016 and GSE167186) were obtained from the Gene Expression Omnibus (GEO), followed by batch effect removal post-merger. The "limma" R package was utilized to identify differentially expressed genes (DEGs). Subsequently, LASSO analysis was conducted on inflammation and pyroptosis-related genes (IPRGs), resulting in the identification of six hub IPRGs. A novel skeletal muscle aging model was developed and validated using an independent dataset. Additionally, Gene Ontology (GO) enrichment analysis was performed on DEGs, along with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene set enrichment analysis (GSEA). ssGSEA was employed to assess differences in immune cell proportions between healthy muscle groups in older versus younger adults. The expression levels of the six core IPRGs were quantified via qRT-PCR.

Results: A total of 44 elderly samples and 68 young healthy samples were analyzed for DEGs. Compared to young healthy muscle tissue, T cell infiltration levels in aged muscle tissue were significantly reduced, while mast cell and monocyte infiltration levels were relatively elevated. A new diagnostic screening model for sarcopenia based on the six IPRGs demonstrated high predictive efficiency (AUC = 0.871). qRT-PCR results indicated that the expression trends of these six IPRGs aligned with those observed in the database.

Conclusion: Six biomarkers-BTG2, FOXO3, AQP9, GPC3, CYCS, and SCN1B-were identified alongside a diagnostic model that offers a novel approach for early diagnosis of sarcopenia.

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来源期刊
Frontiers in Genetics
Frontiers in Genetics Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
5.50
自引率
8.10%
发文量
3491
审稿时长
14 weeks
期刊介绍: Frontiers in Genetics publishes rigorously peer-reviewed research on genes and genomes relating to all the domains of life, from humans to plants to livestock and other model organisms. Led by an outstanding Editorial Board of the world’s leading experts, this multidisciplinary, open-access journal is at the forefront of communicating cutting-edge research to researchers, academics, clinicians, policy makers and the public. The study of inheritance and the impact of the genome on various biological processes is well documented. However, the majority of discoveries are still to come. A new era is seeing major developments in the function and variability of the genome, the use of genetic and genomic tools and the analysis of the genetic basis of various biological phenomena.
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