A panel of blood-based circulatory miRNAs with diagnostic potential in Psoriasis patients

Objective: To explore a set of inflammation associated circulatory miRNAs with potential role in etiopathology of psoriasis as differential disease biomarker/s. Subjects and Methodology: Expression profiling of 15 immunologically relevant miRNA candidates was done on plasma samples from psoriasis vulgaris patients compared to healthy subjects by qRT-PCR. Receiver operating characteristic (ROC) curve was analyzed for significantly altered miRNAs to evaluate their disease diagnostic potential. Correlation analysis among significantly altered miRNAs and their association with disease severity (PASI) was done to validate the candidates as robust disease biomarker/s. Downstream targets and the pathways for each of the significant miRNAs were deciphered using miR target prediction tools and pathway enrichment to elucidate their functional relevance in disease pathogenesis. Results: : 5 miRNAs exhibited a significant change in their expression level among the 15 candidates tested viz miR-215, miR-148a, miR-125b, miR-223 and miR-142-3p. ROCs for all the 5 miRNAs individually as well as in combination exhibited a significant disease discriminatory area under the curve, AUC = 0.762 and p< 0.0001 for all the miRNAs taken together. Statistically, all 5 miRNAs in combination depicted a robust model as disease severity correlate compared to individual miRNAs with highest R 2 value = 0.94 and least AIC score =131.8. Each of the miRNA also exhibited a significant association with at least one of the other miRNAs in the panel. All the 5 miRNAs exhibited functional role in psoriasis immune-pathogenesis in terms of their downstream targets and signaling pathways. Conclusion: In summary our findings identify a panel of blood-based circulatory miRNAs comprising miR-215, miR-148a, miR-125b-5p, miR-223 and miR-142-3p that can differentiate psoriasis vulgaris patients from healthy individuals. In light of the role of each of these miRNAs in modulating immune-inflammatory pathways, the panel provides a rationalized combination of biomarkers that can be tested further on an expanded cohort of patients for its diagnostic value.