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激素性股骨头坏死的生物标志与免疫浸润分析
作者:
作者单位:

郑州大学人民医院

基金项目:

国家自然科学基金项目（面上项目，重点项目，重大项目）


Biomarkers and immune infiltration analysis of steroid-induced necrosis of the femoral head
Author:
Affiliation:

1.People'2.'3.s Hospital of Zhengzhou University

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    摘要:

    [目的]本研究旨在确定参与激素性股骨头坏死(Steroid-induced Osteonecrosis of Femoral Head,SONFH)的潜在长链非编码RNA(lncRNA)和信号通路，并研究其分子机制。[方法]从NCBI-GEO数据库(http://www.ncbi.nlm.nih.gov/geo)下载微阵列数据（GSE123568）,并使用生物信息学工具对其进行了分析。 通过分析差异表达基因（Differential Expressed Genes,DEG）、京都基因和基因组百科全书（KEGG）扩增通路、基因本体论（GO），最后鉴定出蛋白质-蛋白质相互作用（PPI）网络确定了3个关键非编码基因和6个关键mrna。并进一步研究了激素性股骨头坏死mRNAs、miRNAs和lncRNAs的共表达谱，建立了SONFH特异性竞争内源性RNA（ceRNA）网络，分析了免疫浸润，探索了DEG与免疫细胞的相关性。 最后用GSE26316进行验证。[结果]本研究共获得了3个lncRNA（C20orf197 、MIR22HG、XIST）、21个miRNA和37个mRNA，以及一个可能在SONFH中起重要作用的关键轴lncRNA-miRNA-mRNA（XIST/Has-miR-217/FOXO3）。 此外，通过分析其免疫浸润，发现与正常组织相比，SONFH组织含有更多比例的CD4原始T细胞（P <0.05），最后从GSE26316数据集验证了关键基因FOXO3的表达水平。[结论]C20orf197、MIR22HG、XIST是SONFH发病过程中的潜在标志物，基因轴XIST/Has-miR-217/FOXO3在SONFH的发生发展过程中起到重要作用。

    Abstract:

    [Objective] The purpose of this study is to identify the potential long non-coding RNAs (lncRNAs) and signaling pathways involved in Steroid-induced Osteonecrosis of Femoral Head (SONFH), and to investigate their molecular mechanisms.[Methods]Microarray data (GSE123568) were downloaded from NCBI-GEO and analyzed using bioinformatics tools. By analyzing Differentially Expressed Genes (DEG), Kyoto Encyclopedia of Genes and Genomes (KEGG) amplification pathways, Gene Ontology (GO), and finally identified a protein-protein interaction (PPI) network and identified 3 key Noncoding genes and 1 key mRNA. We further studied the co-expression profiles of mRNAs, miRNAs and lncRNAs in steroid-induced necrosis of the femoral head, established a specific competitive endogenous RNA (ceRNA) network for steroid-induced femoral head necrosis, analyzed immune infiltration, and explored the relationship between DEG and immune cells. Correlation. Finally verified with GSE26316.[Results]A total of 3 lncRNAs (C20orf197 MIR22HG XIST), 21 miRNAs and 37 mRNAs, and a key axis lncRNA-miRNA-mRNA (XIST/Has-miR-217/FOXO3) that may play an important role in SONFH were obtained in this study. In addition, by analyzing its immune infiltration, it was found that SONFH tissues contained a higher proportion of CD4 naive T cells compared with normal tissues (P < 0.05), and finally the expression level of the key gene FOXO3 was verified from the GSE26316 dataset. [Conclusion]C20orf197, MIR22HG and XIST are potential markers in the pathogenesis of SONFH, and the gene axis XIST/Has-miR-217/FOXO3 plays an important role in the occurrence and development of SONFH.

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  • 收稿日期:2022-11-07
  • 最后修改日期:2023-01-22
  • 录用日期:2023-03-30
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