Identification of potential miRNA biomarkers for traumatic osteonecrosis of femoral head
Identification of potential miRNA biomarkers for traumatic osteonecrosis of femoral head
复制标题
股骨头外伤性骨坏死潜在 miRNA 生物标志物的鉴定
DOI：
10.1002/jcp.29467
复制
发表时间：
2020-01-17
影响因子：
5.6
通讯作者：
Yang, Pei
中科院分区：
文献类型：
--
作者：
Liu, Guan-Zhi;Chen, Chen;Yang, Pei
创伤性股骨头坏死（TONFH）是髋关节物理损伤引起的骨科常见疾病。然而，由于其发病机制尚不明确，缺乏简单的无创性早期诊断方法，导致大多数患者需要行髋关节置换术。在这项研究中，我们的目的是确定循环microRNAs（miRNAs）的综合生物信息学分析作为潜在的生物标志物的TOFH。mRNA表达谱从Gene Expression Omnibus数据库下载。然后，我们结合了两种miRNA筛选方法：加权基因共表达网络分析和基于倍数变化的差异表达miRNA分析。因此，我们确定了14个关键的miRNAs作为TONFH的潜在生物标志物。此外，还获得了302个miRNAs的靶基因，构建了miRNA-mRNA相互作用网络。此外，京都基因百科全书和基因组通路分析、基因本体功能分析、蛋白质-蛋白质相互作用（PPI）网络分析和PPI网络模块分析结果显示，这14个关键miRNAs与TOFH密切相关。然后建立受试者工作特征曲线，筛选出具有较高诊断价值的6-miRNA特征，包括miR-93 - 5 p（曲线下面积[AUC] = 0.93），miR-1324（AUC = 0.92）、miR-4666 a-3p（AUC = 0.92）、miR-5011 - 3p（AUC = 0.92）和miR-320 a（AUC = 0.89）、miR-185 - 5p（AUC = 0.89）。最后，定量真实的时间聚合酶链反应的结果证实了miR-93 - 5 p和miR-320 a在ONFH患者血清中的显著较高表达。这些循环miRNAs可作为TONFH的候选早期诊断标志物和潜在的治疗靶点。
Traumatic osteonecrosis of femoral head (TONFH) is a common orthopedic disease caused by physical injury in hip. However, the unclear pathogenesis mechanism of TONFH and lacking of simple noninvasive early diagnosis method cause the necessity of hip replacement for most patients with TONFH. In this study, we aimed to identify circulating microRNAs (miRNAs) by integrated bioinformatics analyses as potential biomarker of TONFH. mRNA expression profiles were downloaded from the Gene Expression Omnibus database. Then we combined two miRNA screen methods: Weighted gene co‐expression network analysis and fold change based differentially expressed miRNAs analysis. As a result, we identified 14 key miRNAs as potential biomarkers for TONFH. Besides, 302 target genes of these miRNAs were obtained and the miRNA–mRNA interaction network was constructed. Furthermore, the results of Kyoto Encyclopedia of Gene and Genome pathway analysis, Gene Ontology function analysis, protein–protein interaction (PPI) network analysis and PPI network module analysis showed close correlation between these 14 key miRNAs and TONFH. Then we established receiver operating characteristic curves and identified 6‐miRNA signature with highly diagnosis value including miR‐93‐5p (area under the curve [AUC] = 0.93), miR‐1324 (AUC = 0.92), miR‐4666a‐3p (AUC = 0.92), miR‐5011‐3p (AUC = 0.92), and miR‐320a (AUC = 0.89), miR‐185‐5p (AUC = 0.89). Finally, the results of quantitative real‐time polymerase chain reaction confirmed the significantly higher expression of miR‐93‐5p and miR‐320a in the serum of patients with ONFH. These circulating miRNAs could serve as candidate early diagnosis markers and potential treatment targets of TONFH.