Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas
AuthorCasanova, Nancy G
Gonzalez-Garay, Manuel L
Knox, Kenneth S
Crouser, Elliott D
Garcia, Joe G N
AffiliationUniv Arizona Hlth Sci, Coll Med, Dept Med
Univ Arizona, Coll Med, Dept Med
MetadataShow full item record
CitationCasanova, N. G., Gonzalez-Garay, M. L., Sun, B., Bime, C., Sun, X., Knox, K. S., ... & Garcia, J. G. (2020). Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas. Respiratory Research, 21(1), 1-12.
Rights© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
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AbstractRationale Despite the availability of multi-"omics" strategies, insights into the etiology and pathogenesis of sarcoidosis have been elusive. This is partly due to the lack of reliable preclinical models and a paucity of validated biomarkers. As granulomas are a key feature of sarcoidosis, we speculate that direct genomic interrogation of sarcoid tissues, may lead to identification of dysregulated gene pathways or biomarker signatures. Objective To facilitate the development sarcoidosis genomic biomarkers by gene expression profiling of sarcoidosis granulomas in lung and lymph node tissues (most commonly affected organs) and comparison to infectious granulomas (coccidiodomycosis and tuberculosis). Methods Transcriptomic profiles of immune-related gene from micro-dissected sarcoidosis granulomas within lung and mediastinal lymph node tissues and compared to infectious granulomas from paraffin-embedded blocks. Differentially-expressed genes (DEGs) were profiled, compared among the three granulomatous diseases and analyzed for functional enrichment pathways. Results Despite histologic similarities, DEGs and pathway enrichment markedly differed in sarcoidosis granulomas from lymph nodes and lung. Lymph nodes showed a clear immunological response, whereas a structural regenerative response was observed in lung. Sarcoidosis granuloma gene expression data corroborated previously reported genomic biomarkers (STAB1, HBEGF, and NOTCH4), excluded others and identified new genomic markers present in lung and lymph nodes, ADAMTS1, NPR1 and CXCL2. Comparisons between sarcoidosis and pathogen granulomas identified pathway divergences and commonalities at gene expression level. Conclusion These findings suggest the importance of tissue and disease-specificity evaluation when exploring sarcoidosis genomic markers. This relevant translational information in sarcoidosis and other two histopathological similar infections provides meaningful specific genomic-derived biomarkers for sarcoidosis diagnosis and prognosis.
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Except where otherwise noted, this item's license is described as © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
- Transcriptional Profiling of Endobronchial Ultrasound-Guided Lymph Node Samples Aids Diagnosis of Mediastinal Lymphadenopathy.
- Authors: Tomlinson GS, Thomas N, Chain BM, Best K, Simpson N, Hardavella G, Brown J, Bhowmik A, Navani N, Janes SM, Miller RF, Noursadeghi M
- Issue date: 2016 Feb
- IL-13-regulated Macrophage Polarization during Granuloma Formation in an In Vitro Human Sarcoidosis Model.
- Authors: Locke LW, Crouser ED, White P, Julian MW, Caceres EG, Papp AC, Le VT, Sadee W, Schlesinger LS
- Issue date: 2019 Jan
- Gene expression profiles in granuloma tissue reveal novel diagnostic markers in sarcoidosis.
- Authors: Christophi GP, Caza T, Curtiss C, Gumber D, Massa PT, Landas SK
- Issue date: 2014 Jun
- [Granulomatous diseases and pathogenic microorganism].
- Authors: Inoue Y, Suga M
- Issue date: 2008 Feb
- Evidence for M2 macrophages in granulomas from pulmonary sarcoidosis: A new aspect of macrophage heterogeneity.
- Authors: Shamaei M, Mortaz E, Pourabdollah M, Garssen J, Tabarsi P, Velayati A, Adcock IM
- Issue date: 2018 Jan