基于生物信息学分析探讨股骨头坏死软骨氧化应激相关的枢纽基因及通路。

Identification of Hub Genes and Pathways Associated with Oxidative Stress of Cartilage in Osteonecrosis of Femoral Head Using Bioinformatics Analysis.

机构信息

Department of Orthopedics, General Hospital of Tianjin Medical University, Tianjin, P.R. China.

出版信息

Cartilage. 2022 Jan-Mar;13(1):19476035221074000. doi: 10.1177/19476035221074000.

OBJECTIVE

This study aimed to identify the hub genes and pathways of genes related to oxidative stress of cartilage in osteonecrosis of femoral head (ONFH), and to predict the transcription factors of the hub genes.

METHODS

The GSE74089 was obtained from the Gene Expression Omnibus (GEO) database, including 4 necrotic tissues and 4 normal tissues, and the differentially expressed genes (DEGs) were identified by limma package in R language. Simultaneously, we searched for the genes related to oxidative stress in the Gene Ontology (GO) database. GO and signaling pathways analysis were performed using DAVID, Metascape, and GSEA. Protein-protein interaction (PPI) network was constructed using the STRING database, and the Degree algorithm of Cytoscape software was used to screen for hub genes. Finally, the NetworkAnalyst web tool was used to find the hub genes' transcriptional factors (TFs).

RESULTS

In total, 440 oxidative stress-related genes were found in GSE74089 and GO database, and 88 of them were significantly differentially expressed. These genes were mainly involved in several signaling pathways, such as MAPK signaling pathway, PI3K-AKT-mTOR signaling pathway, FOXO signaling pathway. The top 10 hub genes were JUN, FOXO3, CASP3, JAK2, RELA, EZH2, ABL1, PTGS2, FBXW7, MCL1. Besides, TFAP2A, GATA2, SP1, and E2F1 may be the key regulatory factors of hub genes.

CONCLUSIONS

We identified some hub genes and signaling pathways associated with oxidative stress in ONFH through a series of bioinformatics analyses.

目的

本研究旨在鉴定股骨头坏死（ONFH）软骨氧化应激相关基因的枢纽基因和途径，并预测枢纽基因的转录因子。

方法

从基因表达综合数据库（GEO）中获取 GSE74089 数据集，包含 4 例坏死组织和 4 例正常组织，通过 R 语言中的 limma 包识别差异表达基因（DEGs）。同时，我们在基因本体论（GO）数据库中搜索与氧化应激相关的基因。使用 DAVID、Metascape 和 GSEA 进行 GO 和信号通路分析。使用 STRING 数据库构建蛋白质-蛋白质相互作用（PPI）网络，并使用 Cytoscape 软件的 Degree 算法筛选枢纽基因。最后，使用 NetworkAnalyst 网络工具查找枢纽基因的转录因子（TFs）。

结果

在 GSE74089 和 GO 数据库中总共发现了 440 个与氧化应激相关的基因，其中 88 个基因表达差异显著。这些基因主要参与几个信号通路，如 MAPK 信号通路、PI3K-AKT-mTOR 信号通路、FOXO 信号通路。前 10 个枢纽基因分别为 JUN、FOXO3、CASP3、JAK2、RELA、EZH2、ABL1、PTGS2、FBXW7 和 MCL1。此外，TFAP2A、GATA2、SP1 和 E2F1 可能是枢纽基因的关键调节因子。