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Abstract：
BACKGROUND: Osteoporosis (OP) stands as a prevalent bone ailment affecting the elderly, globally. The identification of reliable diagnostic markers crucially aids OP clinical management.
METHODS: Utilizing the GEO database (GSE35959), we acquired expression profiles for OP and normal samples. Differential expression genes (DEGs) and hub genes were pinpointed through STRING, GEO2R, and Cytoscape. The competing endogenous RNA (ceRNA) network was constructed using miRTarBase, miRDB, and MiRcode databases. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed via DAVID. Validation involved clinical OP samples from the Pakistani population, with Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) assessing hub gene expression.
RESULTS: A total of 2124 differentially expressed genes (DEGs) were identified between OP and normal samples in GSE35959. The selected hub genes among these DEGs were Splicing Factor 3a Subunit 1 (SF3A1), Ataxin 2 Like (ATXN2L), Heat Shock Protein 90 Beta Family Member 1 (HSP90B1), Cluster of Differentiation 74 (CD74), DExH-Box Helicase 29 (DHX29), ALG5 Dolichyl-Phosphate Beta-Glucosyltransferase (ALG5), NudC Domain Containing 2 (NUDCD2), and Ras-related protein Rab-2A (RAB2A). Expression validation of these genes on the Pakistani OP patients revealed significant up-regulation of SF3A1, ATXN2L, and CD74 and significant (P < 0.05) down-regulation of HSP90B1, DHX29, ALG5, NUDCD2, and RAB2A in OP patients. Receiver operating characteristic (ROC) analysis demonstrated that these hub genes displayed considerable diagnostic accuracy for detecting OP. The ceRNA network analysis of the hub genes revealed some important hub genes\' regulatory miRNAs and lncRNAs. Via KEGG analysis, hub genes were found to be enriched in N-Glycan biosynthesis, Thyroid hormone synthesis, IL-17 signaling pathway, Prostate cancer, AMPK signaling pathway, Spliceosome, Estrogen signaling pathway, and Fluid shear stress and atherosclerosis, etc., pathways.
CONCLUSIONS: The identified eight hub genes in the present study could reliably distinguish OP patients from normal individuals, which may provide novel insight into the diagnostic research of OP.
METHODS: Utilizing the GEO database (GSE35959), we acquired expression profiles for OP and normal samples. Differential expression genes (DEGs) and hub genes were pinpointed through STRING, GEO2R, and Cytoscape. The competing endogenous RNA (ceRNA) network was constructed using miRTarBase, miRDB, and MiRcode databases. Gene Ontology (GO) and KEGG pathway enrichment analyses were performed via DAVID. Validation involved clinical OP samples from the Pakistani population, with Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) assessing hub gene expression.
RESULTS: A total of 2124 differentially expressed genes (DEGs) were identified between OP and normal samples in GSE35959. The selected hub genes among these DEGs were Splicing Factor 3a Subunit 1 (SF3A1), Ataxin 2 Like (ATXN2L), Heat Shock Protein 90 Beta Family Member 1 (HSP90B1), Cluster of Differentiation 74 (CD74), DExH-Box Helicase 29 (DHX29), ALG5 Dolichyl-Phosphate Beta-Glucosyltransferase (ALG5), NudC Domain Containing 2 (NUDCD2), and Ras-related protein Rab-2A (RAB2A). Expression validation of these genes on the Pakistani OP patients revealed significant up-regulation of SF3A1, ATXN2L, and CD74 and significant (P < 0.05) down-regulation of HSP90B1, DHX29, ALG5, NUDCD2, and RAB2A in OP patients. Receiver operating characteristic (ROC) analysis demonstrated that these hub genes displayed considerable diagnostic accuracy for detecting OP. The ceRNA network analysis of the hub genes revealed some important hub genes\' regulatory miRNAs and lncRNAs. Via KEGG analysis, hub genes were found to be enriched in N-Glycan biosynthesis, Thyroid hormone synthesis, IL-17 signaling pathway, Prostate cancer, AMPK signaling pathway, Spliceosome, Estrogen signaling pathway, and Fluid shear stress and atherosclerosis, etc., pathways.
CONCLUSIONS: The identified eight hub genes in the present study could reliably distinguish OP patients from normal individuals, which may provide novel insight into the diagnostic research of OP.
摘要：
背景：骨质疏松（OP）是影响老年人的普遍骨骼疾病，全球。可靠的诊断标记物的鉴定对OP临床管理至关重要。
方法：利用GEO数据库（GSE35959），我们获得了OP和正常样本的表达谱。通过STRING确定差异表达基因(DEGs)和hub基因,GEO2R,和Cytoscape。使用miRTarBase构建竞争内源性RNA(ceRNA)网络，miRDB,和MiRcode数据库。通过DAVID进行基因本体论(GO)和KEGG途径富集分析。验证涉及来自巴基斯坦人群的临床OP样本，实时定量聚合酶链反应（RT-qPCR）评估中心基因表达。
结果：在GSE35959中，在OP和正常样品之间共鉴定了2124个差异表达基因（DEGs）。这些DEGs中选择的hub基因是剪接因子3a亚基1（SF3A1），Ataxin2like(ATXN2L),热休克蛋白90β家族成员1(HSP90B1),分化簇74（CD74），DExH-Box解旋酶29(DHX29),ALG5磷酸葡萄糖β-葡萄糖基转移酶（ALG5），NudC域包含2(NUDCD2)，和Ras相关蛋白Rab-2A(RAB2A)。这些基因在巴基斯坦OP患者上的表达验证揭示了SF3A1，ATXN2L的显着上调，在OP患者中，CD74和HSP90B1，DHX29，ALG5，NUDCD2和RAB2A显著下调（P<0.05）。接收器工作特征（ROC）分析表明，这些集线器基因对检测OP具有相当高的诊断准确性。hub基因的ceRNA网络分析揭示了一些重要的hub基因的调控miRNAs和lncRNAs。通过KEGG分析，发现hub基因富含N-聚糖生物合成，甲状腺激素合成,IL-17信号通路,前列腺癌,AMPK信号通路,拼接体,雌激素信号通路,流体剪切应力和动脉粥样硬化，等。,Pathways.
结论：本研究中确定的八个hub基因可以可靠地将OP患者与正常人区分开来，这可能为OP的诊断研究提供新的见解。
方法：利用GEO数据库（GSE35959），我们获得了OP和正常样本的表达谱。通过STRING确定差异表达基因(DEGs)和hub基因,GEO2R,和Cytoscape。使用miRTarBase构建竞争内源性RNA(ceRNA)网络，miRDB,和MiRcode数据库。通过DAVID进行基因本体论(GO)和KEGG途径富集分析。验证涉及来自巴基斯坦人群的临床OP样本，实时定量聚合酶链反应（RT-qPCR）评估中心基因表达。
结果：在GSE35959中，在OP和正常样品之间共鉴定了2124个差异表达基因（DEGs）。这些DEGs中选择的hub基因是剪接因子3a亚基1（SF3A1），Ataxin2like(ATXN2L),热休克蛋白90β家族成员1(HSP90B1),分化簇74（CD74），DExH-Box解旋酶29(DHX29),ALG5磷酸葡萄糖β-葡萄糖基转移酶（ALG5），NudC域包含2(NUDCD2)，和Ras相关蛋白Rab-2A(RAB2A)。这些基因在巴基斯坦OP患者上的表达验证揭示了SF3A1，ATXN2L的显着上调，在OP患者中，CD74和HSP90B1，DHX29，ALG5，NUDCD2和RAB2A显著下调（P<0.05）。接收器工作特征（ROC）分析表明，这些集线器基因对检测OP具有相当高的诊断准确性。hub基因的ceRNA网络分析揭示了一些重要的hub基因的调控miRNAs和lncRNAs。通过KEGG分析，发现hub基因富含N-聚糖生物合成，甲状腺激素合成,IL-17信号通路,前列腺癌,AMPK信号通路,拼接体,雌激素信号通路,流体剪切应力和动脉粥样硬化，等。,Pathways.
结论：本研究中确定的八个hub基因可以可靠地将OP患者与正常人区分开来，这可能为OP的诊断研究提供新的见解。
