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Respir Res ; 21(1): 321, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33276795

RESUMO

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.


Assuntos
Coccidioidomicose/genética , Perfilação da Expressão Gênica , Granuloma/genética , Doenças Linfáticas/genética , Sarcoidose Pulmonar/genética , Transcriptoma , Tuberculose/genética , Adulto , Idoso , Coccidioidomicose/diagnóstico , Coccidioidomicose/imunologia , Coccidioidomicose/microbiologia , Diagnóstico Diferencial , Feminino , Marcadores Genéticos , Granuloma/diagnóstico , Granuloma/imunologia , Granuloma/microbiologia , Humanos , Doenças Linfáticas/diagnóstico , Doenças Linfáticas/imunologia , Masculino , Pessoa de Meia-Idade , Sarcoidose Pulmonar/diagnóstico , Sarcoidose Pulmonar/imunologia , Tuberculose/diagnóstico , Tuberculose/imunologia , Tuberculose/microbiologia , Adulto Jovem
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