Identification of Jak-STAT signaling involvement in sarcoidosis severity via a novel microRNA-regulated peripheral blood mononuclear cell gene signature

• Published in: Scientific reports Vol. 7; no. 1; pp. 4237 - 9
• Main Authors: Zhou, Tong, Casanova, Nancy, Pouladi, Nima, Wang, Ting, Lussier, Yves, Knox, Kenneth S, Garcia, Joe G N
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 26.06.2017; Nature Publishing Group UK; Nature Portfolio
• Subjects: Coronary artery disease; Gene expression; Heart diseases; Lung diseases; MicroRNAs; miRNA; Nervous system; Peripheral blood mononuclear cells; Remission; Sarcoidosis; Signal transduction
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-04109-6

Sarcoidosis is a granulomatous lung disorder of unknown cause. The majority of individuals with sarcoidosis spontaneously achieve full remission (uncomplicated sarcoidosis), however, ~20% of sarcoidosis-affected individuals experience progressive lung disease or cardiac and nervous system involvement (complicated sarcoidosis). We investigated peripheral blood mononuclear cell (PBMC) microRNA and protein-coding gene expression data from healthy controls and patients with uncomplicated or complicated sarcoidosis. We identified 46 microRNAs and 1,559 genes that were differentially expressed across a continuum of sarcoidosis severity (healthy control → uncomplicated sarcoidosis → complicated sarcoidosis). A total of 19 microRNA-mRNA regulatory pairs were identified within these deregulated microRNAs and mRNAs, which consisted of 17 unique protein-coding genes yielding a 17-gene signature. Pathway analysis of the 17-gene signature revealed Jak-STAT signaling pathway as the most significantly represented pathway. A severity score was assigned to each patient based on the expression of the 17-gene signature and a significant increasing trend in the severity score was observed from healthy control, to uncomplicated sarcoidosis, and finally to complicated sarcoidosis. In addition, this microRNA-regulated gene signature differentiates sarcoidosis patients from healthy controls in independent validation cohorts. Our study suggests that PBMC gene expression is useful in diagnosis of sarcoidosis.