Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulomas
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Author
Casanova, Nancy GGonzalez-Garay, Manuel L
Sun, Belinda
Bime, Christian
Sun, Xiaoguang
Knox, Kenneth S
Crouser, Elliott D
Sammani, Nora
Gonzales, Taylor
Natt, Bhupinder
Chaudhary, Sachin
Lussier, Yves
Garcia, Joe G N
Affiliation
Univ Arizona Hlth Sci, Coll Med, Dept MedUniv Arizona, Coll Med, Dept Med
Issue Date
2020-12-04
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Casanova, 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.Journal
RESPIRATORY RESEARCHRights
© 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.Collection Information
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.Abstract
Rationale 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.Note
Open access journalISSN
1465-993XEISSN
1465-993XPubMed ID
33276795Version
Final published versionae974a485f413a2113503eed53cd6c53
10.1186/s12931-020-01537-3
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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.
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