血清外泌体miRNAs标志物预测骨质疏松性椎体压缩性骨折风险
Serum exosomes miRNAs marker predicts osteoporotic vertebral compression fracture risk
  
DOI:10.3969/j.issn.1006-7108.2025.05.009
中文关键词:  骨质疏松症  脊椎  压缩性骨折  外泌体  miRNA
英文关键词:osteoporosis  spine  compression fracture  exosomes  miRNA
基金项目:江西省卫生健康委科技计划项目(202140640)
作者单位
黎细平* 廖勇 刘翔 江西省新余市中医院,江西 新余 338025 
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中文摘要:
      目的 探索老年骨质疏松性脊椎压缩性骨折(osteoporotic vertebral compression fracture,OVCF)患者血清外泌体(Exo)-miRNAs表达特征,构建血清Exo-miRNAs标志物用于评估OVCF风险。方法 选择新余市中医院2021年2月至2024年2月收治的211例OVCF患者和232例骨质疏松症(osteoporosis,OP)患者作为研究对象,并选择医院正常体检的74名健康者作为对照组。对OP、OVCF患者及对照组血清Exo-miRNAs通量测序分析寻找差异表达Exo-miRNAs。利用定量实时聚合酶链反应(RT-qPCR)检测血清Exo-miRNAs表达水平。使用R包multiMiR和Venn图分析miRNAs靶基因并进行基因本体论(GO)、京都基因和基因组(KEGG)及WikiPathway信号通路分析。运用受试者工作特征(ROC)曲线评估Exo-miRNAs标志物预测OVCF风险的临床价值。结果 Exo-miR-4522、miR-1469和miR-4739在对照组、OP和OVCF患者中呈现阶梯式递增(P<0.05)。ROC曲线分析结果显示,血清Exo-miR-4522、miR-1469和miR-4739能有效预测OVCF风险,其曲线下面积(AUC)值均>0.7。3个miRNAs靶基因功能主要富集在库欣综合征、胰岛素抵抗、PI3K-Akt和甲状腺激素产生与外周下游信号传导效应信号通路中。联合ROC曲线构建血清Exo-miR-4522、miR-1469和miR-4739标志物,相较于对照组和OP患者,该标志物预测OVCF风险的AUC分别为0.997(0.968~1.000)和0.944(0.890~0.976),可显著提高OVCF诊断性能。结论 血清Exo-miR-4522、miR-1469和miR-4739可能参与OVCF发病机制。血清Exo-miRNAs标志物是预测OVCF风险的新型生物标志物。
英文摘要:
      Objective To explore the expression characteristics of serum exosomes (Exo)-miRNAs in elderly osteoporotic vertebral compression fracture (OVCF) patients and to construct serum Exo-miRNAs maker for assessing OVCF risk. Methods 211 patients with OVCF and 232 patients with osteoporosis (OP) admitted to our hospital in the year February 2023-February 2024 were selected as study subjects, and 74 healthy individuals with normal physical examination in our hospital were selected as the control group. Serum Exo-miRNAs flux sequencing analysis of OP and OVCF patients and controls was performed to look for differentially expressed Exo-miRNAs.The expression levels of serum Exo-miRNAs were detected using quantitative real-time polymerase chain reaction (RT-qPCR). miRNAs target genes were analyzed and subjected to gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and WikiPathway signaling pathway analysis using the R package multiMiR and Venn diagrams. The clinical value of Exo-miRNAs maker for predicting OVCF risk was assessed using receiver operating characteristic (ROC) curves. Results Exo-miR-4522, miR-1469 and miR-4739 showed a stepwise increase in control, OP and OVCF patients (P<0.05). ROC curve analysis showed that serum Exo-miR-4522, miR-1469 and miR-4739 were effective in predicting the risk of OVCF, and all of them had area under the curve (AUC) values >0.7. The target gene functions of the three miRNAs were mainly enriched in Cushing's syndrome, insulin resistance, PI3K-Akt and thyroid hormone production and peripheral downstream signaling effects signaling pathways. The combined ROC curves constructed serum Exo-miR-4522, miR-1469 and miR-4739 maker, which predicted OVCF risk with AUC of 0.997 (0.968-1.000) and 0.944 (0.890-0.976), respectively, in comparison with control and OP patients, and could significantly improve the diagnostic performance of OVCF. Conclusion Serum Exo-miR-4522, miR-1469 and miR-4739 may be involved in OVCF pathogenesis. maker of serum Exo-miRNAs as novel biomarkers for predicting OVCF risk.
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