Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis

Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ∼20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients wi...

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Main Authors:	Zhou, Tong, Zhang, Wei, Sweiss, Nadera J., Chen, Edward S., Moller, David R., Knox, Kenneth S., Ma, Shwu-Fan, Wade, Michael S., Noth, Imre, Machado, Roberto F., Garcia, Joe G. N.
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3440319/

id	pubmed-3440319
recordtype	oai_dc
spelling	pubmed-34403192012-09-14 Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis Zhou, Tong Zhang, Wei Sweiss, Nadera J. Chen, Edward S. Moller, David R. Knox, Kenneth S. Ma, Shwu-Fan Wade, Michael S. Noth, Imre Machado, Roberto F. Garcia, Joe G. N. Research Article Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ∼20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a 20-gene sarcoidosis biomarker signature distinguishing sarcoidosis (n = 39) from healthy controls (n = 35, 86% classification accuracy) and which served as a molecular signature for complicated sarcoidosis (n = 17). As aberrancies in T cell receptor (TCR) signaling, JAK-STAT (JS) signaling, and cytokine-cytokine receptor (CCR) signaling are implicated in sarcoidosis pathogenesis, a 31-gene signature comprised of T cell signaling pathway genes associated with sarcoidosis (TCR/JS/CCR) was compared to the unbiased 20-gene biomarker signature but proved inferior in prediction accuracy in distinguishing complicated from uncomplicated sarcoidosis. Additional validation strategies included significant association of single nucleotide polymorphisms (SNPs) in signature genes with sarcoidosis susceptibility and severity (unbiased signature genes - CX3CR1, FKBP1A, NOG, RBM12B, SENS3, TSHZ2; T cell/JAK-STAT pathway genes such as AKT3, CBLB, DLG1, IFNG, IL2RA, IL7R, ITK, JUN, MALT1, NFATC2, PLCG1, SPRED1). In summary, this validated peripheral blood molecular gene signature appears to be a valuable biomarker in identifying cases with sarcoidoisis and predicting risk for complicated sarcoidosis. Public Library of Science 2012-09-12 /pmc/articles/PMC3440319/ /pubmed/22984568 http://dx.doi.org/10.1371/journal.pone.0044818 Text en © 2012 Zhou et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Zhou, Tong Zhang, Wei Sweiss, Nadera J. Chen, Edward S. Moller, David R. Knox, Kenneth S. Ma, Shwu-Fan Wade, Michael S. Noth, Imre Machado, Roberto F. Garcia, Joe G. N.
spellingShingle	Zhou, Tong Zhang, Wei Sweiss, Nadera J. Chen, Edward S. Moller, David R. Knox, Kenneth S. Ma, Shwu-Fan Wade, Michael S. Noth, Imre Machado, Roberto F. Garcia, Joe G. N. Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis
author_facet	Zhou, Tong Zhang, Wei Sweiss, Nadera J. Chen, Edward S. Moller, David R. Knox, Kenneth S. Ma, Shwu-Fan Wade, Michael S. Noth, Imre Machado, Roberto F. Garcia, Joe G. N.
author_sort	Zhou, Tong
title	Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis
title_short	Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis
title_full	Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis
title_fullStr	Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis
title_full_unstemmed	Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis
title_sort	peripheral blood gene expression as a novel genomic biomarker in complicated sarcoidosis
description	Sarcoidosis, a systemic granulomatous syndrome invariably affecting the lung, typically spontaneously remits but in ∼20% of cases progresses with severe lung dysfunction or cardiac and neurologic involvement (complicated sarcoidosis). Unfortunately, current biomarkers fail to distinguish patients with remitting (uncomplicated) sarcoidosis from other fibrotic lung disorders, and fail to identify individuals at risk for complicated sarcoidosis. We utilized genome-wide peripheral blood gene expression analysis to identify a 20-gene sarcoidosis biomarker signature distinguishing sarcoidosis (n = 39) from healthy controls (n = 35, 86% classification accuracy) and which served as a molecular signature for complicated sarcoidosis (n = 17). As aberrancies in T cell receptor (TCR) signaling, JAK-STAT (JS) signaling, and cytokine-cytokine receptor (CCR) signaling are implicated in sarcoidosis pathogenesis, a 31-gene signature comprised of T cell signaling pathway genes associated with sarcoidosis (TCR/JS/CCR) was compared to the unbiased 20-gene biomarker signature but proved inferior in prediction accuracy in distinguishing complicated from uncomplicated sarcoidosis. Additional validation strategies included significant association of single nucleotide polymorphisms (SNPs) in signature genes with sarcoidosis susceptibility and severity (unbiased signature genes - CX3CR1, FKBP1A, NOG, RBM12B, SENS3, TSHZ2; T cell/JAK-STAT pathway genes such as AKT3, CBLB, DLG1, IFNG, IL2RA, IL7R, ITK, JUN, MALT1, NFATC2, PLCG1, SPRED1). In summary, this validated peripheral blood molecular gene signature appears to be a valuable biomarker in identifying cases with sarcoidoisis and predicting risk for complicated sarcoidosis.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3440319/
_version_	1611908076335529984

Peripheral Blood Gene Expression as a Novel Genomic Biomarker in Complicated Sarcoidosis

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