Identification of potential miRNA biomarkers for traumatic osteonecrosis of femoral head

• Published in: Journal of cellular physiology Vol. 235; no. 11; pp. 8129 - 8140
• Main Authors: Liu, Guan‐Zhi, Chen, Chen, Kong, Ning, Tian, Run, Li, Yi‐Yang, Li, Zhe, Wang, Kun‐Zheng, Yang, Pei
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.11.2020
• Subjects: Adult; Bioinformatics; Biomarkers; Biomarkers - blood; Biomedical materials; Circulating MicroRNA - blood; Circulating MicroRNA - genetics; Computational Biology; Correlation analysis; Diagnosis; Encyclopedias; Female; Femur; Femur Head - injuries; Femur Head - physiopathology; Function analysis; Gene expression; Gene Expression Profiling; Genomes; Hip; Humans; Male; Microarray Analysis; microRNA expression; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; miRNA; Network analysis; Orthopedics; Osteonecrosis; Osteonecrosis - blood; Osteonecrosis - diagnosis; Osteonecrosis - genetics; Osteonecrosis - physiopathology; Pathogenesis; Polymerase chain reaction; Protein Interaction Maps - genetics; Proteins; Ribonucleic acid; RNA; traumatic osteonecrosis of the femoral head; weighted gene co‐expression network analysis; traumatic osteonecrosis of the femoral head; weighted gene co-expression network analysis; microRNA expression; biomarkers
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.29467

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. We identified 14 key microRNAs (miRNAs) significantly associated with traumatic osteonecrosis of femoral head (TONFH) based on the miRNAs expression profiles from Gene Expression Omnibus database and a six‐miRNA signature with highly diagnosis value was established. The significant upregulation of miR‐93‐5p and miR‐320a were verificated by quantitative real‐time polymerase chain reaction which could serve as potential serum biomarkers of TONFH. Meanwhile, we provide a novel strategy for TONFH diagnosis.