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Serum miRNA-186-3P and miRNA-382-3P constitute a novel Diagnostic miRNA signature for palindromic rheumatism
Fangfang Yuan1, Zefu Weng2, Qiong Yang3
1Department of Rheumatism and Immunology, Ningbo No. 6 Hospital, Ningbo, China.
Background:
Palindromic rheumatism (PR) is a unique disease characterized by the intermittent inflammation of different joints that may progress to a variety of immune-related diseases. Unclear diagnostic criteria have limited the research on its pathogenesis and treatment options. Recently, microRNAs (miRNAs) have been used in the diagnosis of various diseases; however, the role of miRNAs in PR diagnosis remains unexplored. Using next-generation high-throughput sequencing (NGS), this study aimed to screen miRNAs specifically expressed in the serum of patients with PR to construct a miRNA signature and verify its diagnostic efficacy.
Methods:
Patients with PR (N=4), patients with rheumatoid arthritis (RA; N=3), and healthy individuals (Con; N=3) were included in an exploration cohort. Differentially expressed miRNAs were screened using NGS to construct a miRNA signature, and bioinformatics tools were used to perform target gene enrichment analysis of the top 25 differentially expressed miRNAs, both upregulated and downregulated. RT-qPCR was used to verify the differential expression of the miRNA signature in three validation cohorts of patients with PR (N=27) and RA (N=30), and healthy individuals (N=31). The efficiency of the miRNA signature was evaluated using receiver operator characteristic (ROC) curves, an analytical method that assesses diagnostic accuracy.
Results:
A total of 130 miRNAs were differentially expressed in the PR exploration cohort, including 35 upregulated and 95 downregulated compared to levels in the RA and healthy cohorts. miRNA-186-3p showed the largest upregulated difference and miRNA-382-3p the largest downregulated difference; these were selected to construct the miRNA signature. In the ROC curve of the validation cohort, the PR miRNA signature produced an area under the ROC curve (AUC) of 0.980 (95% CI 0.942-1.000) when distinguishing from healthy individuals and of 0.906 (95% CI 0.830-0.983) when distinguishing from RA patients. However, miRNA-186-3p and miRNA-382-3p levels were not associated with disease activity in patients with PR.
Conclusion:
A miRNA signature comprising miRNA-186-3p and miRNA-382-3p can effectively diagnose and differentiate PR from RA. This study provides a basis for the creation of a clinical miRNA signature for the diagnosis of PR.
Insights
This study developed a novel microRNA (miRNA) signature for diagnosing palindromic rheumatism (PR). The signature effectively distinguishes PR from rheumatoid arthritis and healthy individuals, paving the way for improved diagnostic tools.
Area of Science:
- Rheumatology
- Molecular Biology
- Genomics
Background:
- Palindromic rheumatism (PR) is a complex inflammatory condition with unclear diagnostic criteria, hindering research into its causes and treatments.
- MicroRNAs (miRNAs) show promise as diagnostic biomarkers for various diseases, but their role in PR diagnosis is currently unknown.
- This study investigates the potential of serum miRNAs as diagnostic markers for PR.
Purpose of the Study:
- To screen for specific miRNAs in the serum of PR patients using next-generation high-throughput sequencing (NGS).
- To construct a diagnostic miRNA signature for PR.
- To validate the diagnostic efficacy of the developed miRNA signature.
Main Methods:
- Exploration cohort: 4 PR patients, 3 rheumatoid arthritis (RA) patients, 3 healthy controls (Con).
- NGS was used to identify differentially expressed miRNAs; a miRNA signature was constructed using the top 25 miRNAs.
- RT-qPCR validated miRNA expression in three cohorts (27 PR, 30 RA, 31 Con); ROC curves assessed diagnostic accuracy.
Main Results:
- 130 miRNAs were differentially expressed in PR patients compared to RA and healthy controls.
- A miRNA signature was constructed using miRNA-186-3p (upregulated) and miRNA-382-3p (downregulated).
- The miRNA signature achieved an AUC of 0.980 for distinguishing PR from healthy individuals and 0.906 for distinguishing PR from RA patients.
Conclusions:
- A miRNA signature composed of miRNA-186-3p and miRNA-382-3p effectively diagnoses and differentiates PR from RA.
- This study establishes a foundation for a clinical miRNA signature for PR diagnosis.
- The identified miRNAs were not associated with PR disease activity.
