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Differentially expressed microRNAs as diagnostic biomarkers for infected tibial non-union
Yan Dai1, Lili Huang1, Haijun Zhang2
1Department of Infectious Diseases, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Background:
Infected 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.
Methods:
We 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).
Results:
Microarray 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.
Insights
Identifying specific microRNAs (miRNAs) like miR-649, miR-328-5p, and miR-345-3p in bone tissue can aid in diagnosing infected tibial non-union, offering potential new diagnostic and therapeutic tools.
Area of Science:
- Orthopedics
- Molecular Biology
- Biomarker Discovery
Background:
- Infected tibial non-union presents significant clinical challenges, leading to high costs and patient dissatisfaction.
- MicroRNAs (miRNAs) are increasingly recognized for their role in bone disease development.
- Identifying specific miRNA profiles is crucial for novel diagnostic and therapeutic strategies for infected tibial non-union.
Purpose of the Study:
- To identify specific microRNA (miRNA) expression profiles in bone tissue associated with infected tibial non-union.
- To evaluate the diagnostic efficacy of identified miRNAs as potential biomarkers for infected tibial non-union.
Main Methods:
- Microarray analysis was employed to compare miRNA expression in bone tissue between patients with infected tibial non-union and controls.
- Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used to validate microarray findings.
- Receiver operating characteristic (ROC) curve analysis assessed the diagnostic accuracy of candidate miRNAs.
Main Results:
- Microarray analysis revealed 20 differentially expressed miRNAs; six were further validated.
- Specific miRNAs, including miR-649, miR-328-5p, and miR-345-3p, demonstrated significant diagnostic potential with high Area Under the ROC Curve (AUC) values.
- A combination of three miRNAs (miR-649, miR-328-5p, and miR-345-3p) achieved a robust AUC of 0.953 for diagnosing infected tibial non-union.
Conclusions:
- miR-649, miR-328-5p, and miR-345-3p are identified as novel candidate biomarkers for infected tibial non-union.
- These differentially expressed miRNAs hold promise as diagnostic and therapeutic tools for infected tibial non-union.
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