A Circulating Micro-RNA Signature Serves as a Diagnostic and Prognostic Indicator in Sarcoidosis.

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A Circulating Micro-RNA Signature Serves as a Diagnostic and Prognostic Indicator in Sarcoidosis.

Am J Respir Cell Mol Biol. 2017 Aug 16;:

Authors: Ascoli C, Huang Y, Schott C, Turturice BA, Metwally A, Perkins DL, Finn PW, ACCESS Research Group

Abstract
Micro-RNAs (miRNAs) act as post-transcriptional regulators of gene expression. In sarcoidosis, aberrant miRNA expression may enhance immune responses mounted against an unknown antigenic agent. We tested whether a distinct miRNA signature functions as a diagnostic biomarker and explored its role as an immune modulator in sarcoidosis. Expression of miRNAs from peripheral blood mononuclear cells from subjects that met clinical and histopathologic criteria for sarcoidosis were compared to those from matched controls in the ACCESS study. Signature miRNAs were determined by miRNA microarray analysis and validated by quantitative reverse transcription PCR (RT-qPCR). Microarray analysis identified 54 differentially expressed feature mature human miRNAs between groups. Significant feature miRNAs that distinguish sarcoidosis from controls were selected by use of probabilistic models adjusted for clinical variables. Eight signature miRNAs were chosen to verify the diagnosis of sarcoidosis in a validation cohort and distinguished sarcoidosis from controls with a positive predictive value of 88%. We identified both novel and previously described genes and molecular pathways associated with sarcoidosis as targets of these signature miRNAs. Additionally, we demonstrate that signature miRNAs (hsa-miR-150-3p and hsa-miR-342-5p) are significantly associated with reduced lymphocytes and airflow limitations, known markers of poor prognosis. Together, these findings suggest that a circulating miRNA signature serves as a non-invasive biomarker that supports the diagnosis of sarcoidosis. Future studies will test the miRNA signature as a prognostication tool associated with poor clinical outcomes in sarcoidosis.

PMID: 28812922 [PubMed - as supplied by publisher]

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