Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen-specific granulo
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RESEARCH
Differential transcriptomics in sarcoidosis lung and lymph node granulomas with comparisons to pathogen‑specific granulomas Nancy G. Casanova1, Manuel L. Gonzalez‑Garay1, Belinda Sun1, Christian Bime1, Xiaoguang Sun1, Kenneth S. Knox2, Elliott D. Crouser3, Nora Sammani1, Taylor Gonzales1, Bhupinder Natt1, Sachin Chaudhary1, Yves Lussier1 and Joe G. N. Garcia1*
Abstract Rationale: Despite the availability of multi-“omics” strategies, insights into the etiology and pathogenesis of sarcoido‑ sis 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 granulo‑ mas (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. Differ‑ entially-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 regenera‑ tive 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. Keywords: Sarcoidosis, Valley fever, Tuberculosis, Gene expression, Granulomatous, Biomarker
*Correspondence: [email protected] 1 Department of Medicine, College of Medicine, University of Arizona Health Sciences, Tucson, AZ, USA Full list of author information is available at the end of the article
Introduction Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of granulomatous lesions, especially in lung tissues and thoracic lymph
© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permi
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