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Peripheral blood gene expression as a novel genomic biomarker in complicated sarcoidosis.
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- Author(s): Zhou T;Zhou T; Zhang W; Sweiss NJ; Chen ES; Moller DR; Knox KS; Ma SF; Wade MS; Noth I; Machado RF; Garcia JG
- Source:
PloS one [PLoS One] 2012; Vol. 7 (9), pp. e44818. Date of Electronic Publication: 2012 Sep 12.- Publication Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't- Language:
English - Source:
- Additional Information
- Source: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
- Publication Information: Original Publication: San Francisco, CA : Public Library of Science
- Subject Terms: Gene Expression Regulation*; Biomarkers/*metabolism ; Sarcoidosis/*blood ; Sarcoidosis/*genetics; Adult ; Case-Control Studies ; Female ; Gene Expression Profiling ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genomics ; Humans ; Male ; Middle Aged ; Models, Biological ; Oligonucleotide Array Sequence Analysis ; Receptors, Antigen, T-Cell/metabolism ; Signal Transduction
- Abstract: 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.
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Clin Exp Immunol. 2006 Mar;143(3):420-6. (PMID: 16487240) - Grant Information: U01 HL105371 United States HL NHLBI NIH HHS; HL68019 United States HL NHLBI NIH HHS; K23 HL098454 United States HL NHLBI NIH HHS; RC2 HL101740-01 United States HL NHLBI NIH HHS; U01HL105371-01 United States HL NHLBI NIH HHS; R01 HL068019 United States HL NHLBI NIH HHS; NHLBI K23HL098454 United States PHS HHS; R01HL112051 United States HL NHLBI NIH HHS; HL83870 United States HL NHLBI NIH HHS; RC2 HL101740 United States HL NHLBI NIH HHS; NHLBI HL58094 United States PHS HHS; R01 HL083870 United States HL NHLBI NIH HHS
- Accession Number: 0 (Biomarkers)
0 (Receptors, Antigen, T-Cell) - Publication Date: Date Created: 20120918 Date Completed: 20130312 Latest Revision: 20211021
- Publication Date: 20221213
- Accession Number: PMC3440319
- Accession Number: 10.1371/journal.pone.0044818
- Accession Number: 22984568
- Source:
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