揭示代谢功能障碍相关性脂肪肝中 WGCNA 确定的氧化应激相关枢纽基因的功能，并对其进行双样本亡羊补牢式随机分析

IF 2.3 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemistry and Biophysics Reports Pub Date : 2024-09-22 DOI:10.1016/j.bbrep.2024.101829

Qian Zhu , Jiaqi Liu , Wuxuan Mei , Changchun Zeng

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引用次数: 0

摘要

代谢功能障碍相关性脂肪肝（MAFLD）在氧化应激（OS）的影响下加速发展。鉴定代谢功能障碍相关脂肪肝中与氧化应激相关的生物标志物并探索其潜在的机理研究势在必行。本研究的目的是鉴定 MAFLD 中与 OS 相关的生物标志物，并探索其潜在机制。利用GSE17470和GSE24807数据集进行了DEG分析。利用WGCNA进行了调查性探索，以阐明与OS相关的枢纽基因。通过WGCNA确定的OS相关枢纽基因与DEG的交叉点被系统地用于全面分析。一项孟德尔随机化（MR）研究考察了C反应蛋白（CRP）对MAFLD的因果效应。在 MAFLD 中发现了 59 个与 OS 相关的 DEGs。WGCNA揭示了MAFLD中100个与OS相关的枢纽基因。16个OS相关基因被确定为MAFLD中的关键成分。利用 GO 和 KEGG 通路进行的富集分析发现了这些基因富集的通路。在进行 PPI 分析后，确定了表现出异常表达的排名最高的十个中心基因。最终，双样本 MR 分析表明，中枢基因 CRP 与 MAFLD 的发生之间存在因果关系。在这项研究中，我们利用 WGCNA 建立了共表达网络，并确定了 MAFLD 中与操作系统相关的枢纽 DEGs。此外，枢纽基因 CRP 与 MAFLD 的易感性有显著相关性。这些发现为OS相关基因在MAFLD患者中的应用提供了创新视角。

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Unveiling functionality and conducting two-sample mendelian randomization on WGCNA-identified oxidative stress-related hub genes in metabolic dysfunction-associated fatty liver disease

Metabolic dysfunction-associated fatty liver disease (MAFLD) shows accelerated development under the impact of oxidative stress (OS). There is an imperative to identify OS-related biomarkers in MAFLD and explore their potential mechanistic insights. The objective of this study was to identify OS-related biomarkers in MAFLD and explore their potential mechanisms. DEG analysis was performed using GSE17470 and GSE24807 datasets. An investigative exploration utilizing WGCNA was executed to elucidate hub OS-related genes. The intersection of OS-related hub genes identified by WGCNA and DEGs was systematically employed for thorough analyses. A mendelian randomization (MR) study examined the causal effect of C-reactive protein (CRP) on MAFLD. 59 OS-related DEGs were identified in MAFLD. WGCNA revealed 100 OS-related hub genes in MAFLD. Sixteen OS-related genes have been delineated as critical components in MAFLD. Enrichment analyses, employing GO and KEGG pathways, revealed pathways enriched with these genes. Following PPI analyses, the highest-ranking ten hub genes demonstrating abnormal expression were determined. Ultimately, a two-sample MR analysis demonstrated a causal link between the hub gene CRP and the occurrence of MAFLD. In this study, we harnessed WGCNA to formulate a co-expression network and identified hub OS-related DEGs in MAFLD. Additionally, the hub gene CRP exhibited a significant correlation with the predisposition to MAFLD. These findings offer innovative perspectives on the applications of OS-associated genes in individuals afflicted with MAFLD.

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来源期刊

Biochemistry and Biophysics Reports Biochemistry, Genetics and Molecular Biology-Biophysics

CiteScore

4.60

自引率

0.00%

发文量

191

审稿时长

59 days

期刊介绍： Open access, online only, peer-reviewed international journal in the Life Sciences, established in 2014 Biochemistry and Biophysics Reports (BB Reports) publishes original research in all aspects of Biochemistry, Biophysics and related areas like Molecular and Cell Biology. BB Reports welcomes solid though more preliminary, descriptive and small scale results if they have the potential to stimulate and/or contribute to future research, leading to new insights or hypothesis. Primary criteria for acceptance is that the work is original, scientifically and technically sound and provides valuable knowledge to life sciences research. We strongly believe all results deserve to be published and documented for the advancement of science. BB Reports specifically appreciates receiving reports on: Negative results, Replication studies, Reanalysis of previous datasets.