基于 WGCNA 的非酒精性脂肪性肝病关键基因及通路的鉴定。

WGCNA-Based Identification of Hub Genes and Key Pathways Involved in Nonalcoholic Fatty Liver Disease.

机构信息

Second Clinical Medical College, Guangzhou University of Chinese Medicine, 232 Waihuan Road E, Guangzhou, Guangdong 510006, China.

Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong 510120, China.

出版信息

Biomed Res Int. 2021 Dec 13;2021:5633211. doi: 10.1155/2021/5633211. eCollection 2021.

BACKGROUND

The morbidity of nonalcoholic fatty liver disease (NAFLD) has been rising, but the pathogenesis of NAFLD is still elusive. This study is aimed at determining NAFLD-related hub genes based on weighted gene coexpression network analysis (WGCNA).

METHODS

GSE126848 dataset based construction of coexpression networks was performed based on WGCNA. Database for Annotation, Visualization, and Integrated Discovery (DAVID) was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Hub genes were identified and validated in independent datasets and mouse model.

RESULTS

We found that the steelblue module was most significantly correlated with NAFLD. Total 15 hub genes (NDUFA9, UQCRQ, NDUFB8, COPS5, RPS17, UBL5, PSMA3, PSMA1, SF3B5, MRPL27, RPL26, PDCD5, PFDN6, SNRPD2, PSMB3) were derived from both the coexpression and PPI networks and considered "true" hub genes. Functional enrichment analysis showed that the hub genes were related to NAFLD pathway and oxidative phosphorylation. Independent dataset-based analysis and the establishment of NAFLD mouse model confirmed the involvement of two hub genes NDUFA9 and UQCRQ in the pathogenesis of NAFLD.

CONCLUSIONS

Oxidative phosphorylation and NAFLD pathway may be crucially involved in the pathogenesis of NAFLD, and two hub genes NDUFA9 and UQCRQ might be diagnostic biomarkers and therapeutic targets for NAFLD.

背景

非酒精性脂肪性肝病（NAFLD）的发病率一直在上升，但 NAFLD 的发病机制仍不清楚。本研究旨在通过加权基因共表达网络分析（WGCNA）确定与 NAFLD 相关的枢纽基因。

方法

基于 WGCNA 构建共表达网络，使用基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析数据库（DAVID）进行分析。在独立数据集和小鼠模型中鉴定和验证枢纽基因。

结果

我们发现steelblue 模块与 NAFLD 相关性最强。总共确定了 15 个枢纽基因（NDUFA9、UQCRQ、NDUFB8、COPS5、RPS17、UBL5、PSMA3、PSMA1、SF3B5、MRPL27、RPL26、PDCD5、PFDN6、SNRPD2、PSMB3），它们既来自共表达网络，也来自蛋白质-蛋白质相互作用网络，被认为是“真正的”枢纽基因。功能富集分析表明，这些枢纽基因与 NAFLD 通路和氧化磷酸化有关。基于独立数据集的分析和 NAFLD 小鼠模型的建立证实了两个枢纽基因 NDUFA9 和 UQCRQ 参与了 NAFLD 的发病机制。