Deng Ya-Jun, Li Zhi, Wang Bo, Li Jie, Ma Jun, Xue Xiong, Tian Xin, Liu Quan-Cheng, Zhang Ying, Yuan Bin
Department of Spine Surgery, Xi'an Daxing Hospital, Yanan University, Xi'an, China.
Front Genet. 2023 Aug 4;14:1219894. doi: 10.3389/fgene.2023.1219894. eCollection 2023.
Bone immune disorders are major contributors to osteoporosis development. This study aims to identify potential diagnostic markers and molecular targets for osteoporosis treatment from an immunological perspective. We downloaded dataset GSE56116 from the Gene Expression Omnibus database, and identified differentially expressed genes (DEGs) between normal and osteoporosis groups. Subsequently, differentially expressed immune-related genes (DEIRGs) were identified, and a functional enrichment analysis was performed. A protein-protein interaction network was also constructed based on data from STRING database to identify hub genes. Following external validation using an additional dataset (GSE35959), effective biomarkers were confirmed using RT-qPCR and immunohistochemical (IHC) staining. ROC curves were constructed to validate the diagnostic values of the identified biomarkers. Finally, a ceRNA and a transcription factor network was constructed, and a Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed to explore the biological functions of these diagnostic markers. In total, 307 and 31 DEGs and DEIRGs were identified, respectively. The enrichment analysis revealed that the DEIRGs are mainly associated with Gene Ontology terms of positive regulation of MAPK cascade, granulocyte chemotaxis, and cytokine receptor. protein-protein interaction network analysis revealed 10 hub genes: , , , , , , , , , . The expression level of was also found to be significantly high. RT-qPCR and immunohistochemical results showed that the expression of was significantly higher in osteoporosis patients compared to the normal group, as evidenced by the area under the curve Area Under Curve of 0.802. Then, we constructed -hsa-miR-128-3p-, and -hsa-miR-128-3p- ceRNA networks in addition to -, -, - and - transcriptional networks. Finally, functional enrichment analysis revealed that was involved in the development and progression of osteoporosis by regulating local immune and inflammatory processes in bone tissue. This study identifies the immune-related gene as a diagnostic marker of osteoporosis from an immunological perspective, and provides insight into its biological function.
骨免疫紊乱是骨质疏松症发展的主要因素。本研究旨在从免疫学角度确定骨质疏松症治疗的潜在诊断标志物和分子靶点。我们从基因表达综合数据库下载了数据集GSE56116，并鉴定了正常组和骨质疏松组之间的差异表达基因（DEG）。随后，鉴定了差异表达的免疫相关基因（DEIRG），并进行了功能富集分析。还基于STRING数据库的数据构建了蛋白质-蛋白质相互作用网络，以鉴定枢纽基因。使用另一个数据集（GSE35959）进行外部验证后，通过RT-qPCR和免疫组织化学（IHC）染色确认了有效的生物标志物。构建ROC曲线以验证所鉴定生物标志物的诊断价值。最后，构建了ceRNA和转录因子网络，并进行了基因本体论和京都基因与基因组百科全书富集分析，以探索这些诊断标志物的生物学功能。总共分别鉴定出307个和31个DEG和DEIRG。富集分析表明，DEIRG主要与MAPK级联反应的正调控、粒细胞趋化性和细胞因子受体的基因本体学术语相关。蛋白质-蛋白质相互作用网络分析揭示了10个枢纽基因：……（此处原文未给出具体基因名称）。还发现……（此处原文未给出具体基因名称）的表达水平显著较高。RT-qPCR和免疫组织化学结果表明，与正常组相比，骨质疏松症患者中……（此处原文未给出具体基因名称）的表达显著更高，曲线下面积为0.802证明了这一点。然后，除了……（此处原文未给出具体基因名称）转录网络外，我们还构建了……（此处原文未给出具体基因名称）-hsa-miR-128-3p-和……（此处原文未给出具体基因名称）-hsa-miR-128-3p-ceRNA网络。最后，功能富集分析表明，……（此处原文未给出具体基因名称）通过调节骨组织中的局部免疫和炎症过程参与骨质疏松症的发生和发展。本研究从免疫学角度将免疫相关基因……（此处原文未给出具体基因名称）鉴定为骨质疏松症的诊断标志物，并深入了解了其生物学功能。
