生物信息学分析及鉴定激素性股骨头坏死相关基因和分子通路。

Bioinformatics analysis and identification of genes and molecular pathways in steroid-induced osteonecrosis of the femoral head.

机构信息

The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.

Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, China.

出版信息

J Orthop Surg Res. 2021 May 20;16(1):327. doi: 10.1186/s13018-021-02464-9.

DOI:10.1186/s13018-021-02464-9

PMID:34016144

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8136174/

Abstract

BACKGROUND

Steroid-induced osteonecrosis of the femoral head (ONFH) is a common hip joint disease and is difficult to be diagnosed early. At present, the pathogenesis of steroid-induced ONFH remains unclear, and recognized and effective diagnostic biomarkers are deficient. The present study aimed to identify potentially important genes and signaling pathways involved in steroid-induced ONFH and investigate their molecular mechanisms.

METHODS

Microarray data sets GSE123568 (peripheral blood) and GSE74089 (cartilage) were obtained from the Gene Expression Omnibus database, including 34 ONFH samples and 14 control samples. Morpheus software and Venn diagram were used to identify DEGs and co-expressed DEGs, respectively. Besides, we conducted Kyoto Encyclopedia of Genome (KEGG) and gene ontology (GO) pathway enrichment analysis. We construct a protein-protein interaction (PPI) network through GEO2R and used cytoHubba to divide the PPI network into multiple sub-networks. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to verify the bioinformatics analysis results.

RESULTS

A total of 118 intersecting DEGs were obtained between the peripheral blood and cartilage samples, including 40 upregulated genes and 78 downregulated genes. Then, GO and KEGG pathway enrichment analysis revealed that upregulated DEGs focused on the signaling pathways related to staphylococcus aureus infection, leishmaniasis, antigen processing, and presentation, as well as asthma and graft-versus-host disease. Downregulated genes were concentrated in the FoxO signaling pathway, AMPK signaling pathway, signaling pathway regulating stem cell pluripotency, and mTOR signaling pathway. Some hub genes with high interactions such as CXCR1, FPR1, MAPK1, FOXO3, FPR2, CXCR2, and TYROBP were identified in the PPI network. The results of qRT-PCR demonstrated that CXCR1, FPR1, and TYROBP were upregulated while MAPK1 was downregulated in peripheral blood of steroid-induced ONFH patients. This was consistent with the bioinformatics analysis.

CONCLUSIONS

The present study would provide novel insight into the genes and associated pathways involved in steroid-induced ONFH. CXCR1, FPR1, TYROBP, and MAPK1 may be used as potential drug targets and biomarkers for the diagnosis and prognosis of steroid-induced ONFH.

摘要

背景

激素诱导性股骨头坏死（ONFH）是一种常见的髋关节疾病，早期诊断困难。目前，激素诱导性 ONFH 的发病机制尚不清楚，也缺乏公认的有效诊断生物标志物。本研究旨在鉴定与激素诱导性 ONFH 相关的潜在重要基因和信号通路，并探讨其分子机制。

方法

从基因表达综合数据库中获取了微阵列数据集 GSE123568（外周血）和 GSE74089（软骨），包括 34 例 ONFH 样本和 14 例对照样本。Morpheus 软件和 Venn 图分别用于鉴定差异表达基因（DEGs）和共表达 DEGs。此外，还进行了京都基因与基因组百科全书（KEGG）和基因本体论（GO）通路富集分析。通过 GEO2R 构建蛋白质-蛋白质相互作用（PPI）网络，并使用 cytoHubba 将 PPI 网络划分为多个子网络。此外，还进行了定量实时聚合酶链反应（qRT-PCR）以验证生物信息学分析结果。

结果

从外周血和软骨样本中获得了 118 个相交的 DEGs，包括 40 个上调基因和 78 个下调基因。然后，GO 和 KEGG 通路富集分析表明，上调的 DEGs 主要集中在与金黄色葡萄球菌感染、利什曼病、抗原加工和呈递以及哮喘和移植物抗宿主病相关的信号通路。下调基因集中在 FoxO 信号通路、AMPK 信号通路、调节干细胞多能性的信号通路和 mTOR 信号通路。在 PPI 网络中鉴定出一些具有高相互作用的枢纽基因，如 CXCR1、FPR1、MAPK1、FOXO3、FPR2、CXCR2 和 TYROBP。qRT-PCR 结果表明，激素诱导性 ONFH 患者外周血中 CXCR1、FPR1 和 TYROBP 上调，而 MAPK1 下调。这与生物信息学分析结果一致。