Differentially expressed microRNAs as diagnostic biomarkers for infected tibial non-union

Abstract

BackgroundInfected tibial non-union is a challenging clinical complication of fracture treatment. Improper treatment of infected tibial non-union may result in high treatment costs and a long treatment period, and lead to medical disputes and decreased patient satisfaction. An increasing number of studies have indicated the significant role of microRNAs (miRNAs) in the development and progression of different bone diseases. Therefore, the identification of a specific miRNA expression profile associated with infected tibial non-union is a key step toward establishing a novel strategy for the diagnosis and treatment of infected tibial non-union. MethodsWe utilised a microarray analysis to compare the specific expression of bone tissue miRNA in patients with infected tibial non-union and closed tibial fractures. Quantitative real-time reverse transcription-polymerase chain reaction was performed to validate the microarray results. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic efficacy of the identified regulated miRNA(s) isolated from bone tissue as potential biomarker(s). ResultsMicroarray analysis showed 20 differentially expressed miRNAs. Differential expression of miR-649, miR-29b-3p, miR-498, miR-365a-5p, miR-328-5p, and miR-345-3p was further confirmed in a validation cohort. ROC curve analyses showed an AUC (Areas Under the ROC Curve) of 0.808 (95% confidence interval [CI]: 0.675-0.940), 0.778 (95% CI: 0.634-0.921), 0.769 (95% CI: 0.619-0.919), 0.798 (95% CI: 0.662-0.933), 0.818 (95% CI: 0.690-0.945), 0.839 (95% CI: 0.715-0.963) for miR-649, miR-29b-3p, miR-498, miR-365a-5p, miR-328-5p, and miR-345-3p, respectively. The combined use of three miRNAs (miR-649, miR-328-5p, and miR-345-3p) yielded an overall diagnostic accuracy of AUC = 0.953, indicating a robust diagnostic value. Conclusion: Our findings highlight the role of miR-649, miR-328-5p, and miR-345-3p as novel candidate biomarkers for infected tibial non-union diagnosis, suggesting that these differentially expressed miRNAs could be utilised as novel diagnostic and therapeutic tools to identify infected tibial non-union.