Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| DOI: | 10.3389/fmicb.2016.01586 |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/18138 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ. Brasil. |
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Araujo, Leonardo S. deVaas, Lea A. I.Alves, Marcelo RibeiroGeffers, RobertMello, Fernanda C. Q.Almeida, Alexandre S. deMoreira, Adriana da S. R.Kritski, Afrânio L.Silva, José R. Lapa eMoraes, Milton O.Pessler, FrankSaad, Maria H. F.2017-03-23T15:31:21Z2017-03-23T15:31:21Z2016ARAUJO, Leonardo S. de; et al. ranscriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood. Frontiers in Microbiology, v.7, Article1586,10p, Oct. 2016.1664-302Xhttps://www.arca.fiocruz.br/handle/icict/1813810.3389/fmicb.2016.01586engFrontiers MediaTuberculoseBiomarcadoresTuberculosisBiomarkersTranscriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Bloodinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ. Brasil.TWINCORE. Center for Experimental and Clinical Infection Research. Hannover, Germany.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Pesquisa Clínica em DST-AIDS. Rio de janeiro, RJ, Brasil.Helmholtz Centre for Infection Research. Braunschweig, Germany.Universidade Federal do Rio de Janeiro. Instituto de Doenças Torácicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Instituto de Doenças Torácicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Doenças Torácicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Doenças Torácicas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Hanseníase. Rio de Janeiro, RJ. Brasil.TWINCORE. Center for Experimental and Clinical Infection Research. Hannover, Germany / Helmholtz Centre for Infection Research. Braunschweig, Germany..Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ. Brasil.Lately, much effort has been made to find mRNA biomarkers for tuberculosis (TB) disease/infection with microarray-based approaches. In a pilot investigation, through RNA sequencing technology, we observed a prominent modulation of DOCK9, EPHA4, and NPC2 mRNA abundance in the blood of TB patients. To corroborate these findings, independent validations were performed in cohorts from different areas. Gene expression levels in blood were evaluated by quantitative real-time PCR (Brazil, n = 129) or reanalysis of public microarray data (UK: n = 96; South Africa: n = 51; Germany: n = 26; and UK/France: n = 63). In the Brazilian cohort, significant modulation of all target-genes was observed comparing TB vs. healthy recent close TB contacts (rCt). With a 92% specificity, NPC2 mRNA high expression (NPC2(high)) showed the highest sensitivity (85%, 95% CI 65%-96%; area under the ROC curve [AUROC] = 0.88), followed by EPHA4 (53%, 95% CI 33%-73%, AUROC = 0.73) and DOCK9 (19%, 95% CI 7%-40%; AUROC = 0.66). All the other reanalyzed cohorts corroborated the potential of NPC2(high) as a biomarker for TB (sensitivity: 82-100%; specificity: 94-97%). An NPC2(high) profile was also observed in 60% (29/48) of the tuberculin skin test positive rCt, and additional follow-up evaluation revealed changes in the expression levels of NPC2 during the different stages of Mycobacterium tuberculosis infection, suggesting that further studies are needed to evaluate modulation of this gene during latent TB and/or progression to active disease. Considering its high specificity, our data indicate, for the first time, that NPC2(high) might serve as an accurate single-gene biomarker for TB.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/18138/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALmaria_saad_etal_IOC_2016.pdfmaria_saad_etal_IOC_2016.pdfapplication/pdf1442168https://www.arca.fiocruz.br/bitstream/icict/18138/2/maria_saad_etal_IOC_2016.pdf43c9972625d9833582c575a53ab4d36bMD52TEXTmaria_saad_etal_IOC_2016.pdf.txtmaria_saad_etal_IOC_2016.pdf.txtExtracted texttext/plain49722https://www.arca.fiocruz.br/bitstream/icict/18138/3/maria_saad_etal_IOC_2016.pdf.txt1f7a3cdfc1d620a2bd0a6ad49b0428b2MD53icict/181382018-08-15 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| dc.title.pt_BR.fl_str_mv |
Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood |
| title |
Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood |
| spellingShingle |
Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood Araujo, Leonardo S. de Tuberculose Biomarcadores Tuberculosis Biomarkers |
| title_short |
Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood |
| title_full |
Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood |
| title_fullStr |
Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood |
| title_full_unstemmed |
Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood |
| title_sort |
Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood |
| author |
Araujo, Leonardo S. de |
| author_facet |
Araujo, Leonardo S. de Vaas, Lea A. I. Alves, Marcelo Ribeiro Geffers, Robert Mello, Fernanda C. Q. Almeida, Alexandre S. de Moreira, Adriana da S. R. Kritski, Afrânio L. Silva, José R. Lapa e Moraes, Milton O. Pessler, Frank Saad, Maria H. F. |
| author_role |
author |
| author2 |
Vaas, Lea A. I. Alves, Marcelo Ribeiro Geffers, Robert Mello, Fernanda C. Q. Almeida, Alexandre S. de Moreira, Adriana da S. R. Kritski, Afrânio L. Silva, José R. Lapa e Moraes, Milton O. Pessler, Frank Saad, Maria H. F. |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Araujo, Leonardo S. de Vaas, Lea A. I. Alves, Marcelo Ribeiro Geffers, Robert Mello, Fernanda C. Q. Almeida, Alexandre S. de Moreira, Adriana da S. R. Kritski, Afrânio L. Silva, José R. Lapa e Moraes, Milton O. Pessler, Frank Saad, Maria H. F. |
| dc.subject.other.pt_BR.fl_str_mv |
Tuberculose Biomarcadores |
| topic |
Tuberculose Biomarcadores Tuberculosis Biomarkers |
| dc.subject.en.pt_BR.fl_str_mv |
Tuberculosis Biomarkers |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ. Brasil. |
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2016 |
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2016 |
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2017-03-23T15:31:21Z |
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2017-03-23T15:31:21Z |
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info:eu-repo/semantics/publishedVersion |
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ARAUJO, Leonardo S. de; et al. ranscriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood. Frontiers in Microbiology, v.7, Article1586,10p, Oct. 2016. |
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https://www.arca.fiocruz.br/handle/icict/18138 |
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1664-302X |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fmicb.2016.01586 |
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ARAUJO, Leonardo S. de; et al. ranscriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood. Frontiers in Microbiology, v.7, Article1586,10p, Oct. 2016. 1664-302X 10.3389/fmicb.2016.01586 |
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