Transcriptomic biomarkers for tuberculosis: Validation of npc2 as a single mrna biomarker to diagnose tb, predict disease progression, and monitor treatment response
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
Texto Completo: | https://www.arca.fiocruz.br/handle/icict/50271 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil / TWINCORE Centre for Experimental and Clinical Infection Research. Research Group Biomarkers for Infectious Diseases. Hannover, Germany. |
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Araujo, Leonardo S. deRibeiro-Alves, MarceloWipperman, Matthew F.Vorkas, Charles KyriakosPessler, FrankSaad, Maria Helena Féres2021-12-09T22:14:22Z2021-12-09T22:14:22Z2021ARAUJO, Leonardo S. et al. Transcriptomic Biomarkers for Tuberculosis: Validation of NPC2 as a Single mRNA Biomarker to Diagnose TB, Predict Disease Progression, and Monitor Treatment Response. Cells vol. 10, n. 10, p. 1-18, 20212073-4409https://www.arca.fiocruz.br/handle/icict/5027110.3390/cells10102704engMDPITranscriptomic biomarkers for tuberculosis: Validation of npc2 as a single mrna biomarker to diagnose tb, predict disease progression, and monitor treatment responseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil / TWINCORE Centre for Experimental and Clinical Infection Research. Research Group Biomarkers for Infectious Diseases. Hannover, Germany.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Immunology Program, Memorial Sloan Kettering Cancer Center. New York, NY, USA / Weill Cornell Medicine. Clinical and Translational Science Center. New York, NY, USA.Immunology Program, Memorial Sloan Kettering Cancer Center. New York, NY, USA / Stony Brook University. Division of Infectious Diseases, Renaissance School of Medicine. Stony Brook, NY, USA.TWINCORE Centre for Experimental and Clinical Infection Research. Research Group Biomarkers for Infectious Diseases. Hannover, Germany / Centre for Individualised Infection Medicine. Hannover, Germany / Helmholtz Center for Infection Research. Braunschweig, Germany.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.External validation in different cohorts is a key step in the translational development of new biomarkers. We previously described three host mRNA whose expression in peripheral blood is significantly higher (NPC2) or lower (DOCK9 and EPHA4) in individuals with TB compared to latent TB infection (LTBI) and controls. We have now conducted an independent validation of these genes by re-analyzing publicly available transcriptomic datasets from Brazil, China, Haiti, India, South Africa, and the United Kingdom. Comparisons between TB and control/LTBI showed significant differential expression of all three genes (NPC2high p < 0.01, DOCK9low p < 0.01, and EPHA4low p < 0.05). NPC2high had the highest mean area under the ROC curve (AUROC) for the differentiation of TB vs. controls (0.95) and LTBI (0.94). In addition, NPC2 accurately distinguished TB from the clinically similar conditions pneumonia (AUROC, 0.88), non-active sarcoidosis (0.87), and lung cancer (0.86), but not from active sarcoidosis (0.66). Interestingly, individuals progressing from LTBI to TB showed a constant increase in NPC2 expression with time when compared to non-progressors (p < 0.05), with a significant change closer to manifestation of active disease (≤3 months, p = 0.003). Moreover, NPC2 expression normalized with completion of anti-TB treatment. Taken together, these results validate NPC2 mRNA as a diagnostic host biomarker for active TB independent of host genetic background. Moreover, they reveal its potential to predict progression from latent to active infection and to indicate a response to anti-TB treatment.Mycobacterium tuberculosisNPC2Niemann–Pick disease type C2RNABiomarkersDiagnosismRNATranscriptionTreatmentTuberculosisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83099https://www.arca.fiocruz.br/bitstream/icict/50271/1/license.txt586c046dcfeef936e32f0323bb9a47c0MD51ORIGINALTranscriptomic_Marcelo_Alves_etal_INI_2021.pdfTranscriptomic_Marcelo_Alves_etal_INI_2021.pdfapplication/pdf1906073https://www.arca.fiocruz.br/bitstream/icict/50271/2/Transcriptomic_Marcelo_Alves_etal_INI_2021.pdf521271c432cac07d51ba16f2b018ca74MD52icict/502712021-12-09 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dc.title.pt_BR.fl_str_mv |
Transcriptomic biomarkers for tuberculosis: Validation of npc2 as a single mrna biomarker to diagnose tb, predict disease progression, and monitor treatment response |
title |
Transcriptomic biomarkers for tuberculosis: Validation of npc2 as a single mrna biomarker to diagnose tb, predict disease progression, and monitor treatment response |
spellingShingle |
Transcriptomic biomarkers for tuberculosis: Validation of npc2 as a single mrna biomarker to diagnose tb, predict disease progression, and monitor treatment response Araujo, Leonardo S. de Mycobacterium tuberculosis NPC2 Niemann–Pick disease type C2 RNA Biomarkers Diagnosis mRNA Transcription Treatment Tuberculosis |
title_short |
Transcriptomic biomarkers for tuberculosis: Validation of npc2 as a single mrna biomarker to diagnose tb, predict disease progression, and monitor treatment response |
title_full |
Transcriptomic biomarkers for tuberculosis: Validation of npc2 as a single mrna biomarker to diagnose tb, predict disease progression, and monitor treatment response |
title_fullStr |
Transcriptomic biomarkers for tuberculosis: Validation of npc2 as a single mrna biomarker to diagnose tb, predict disease progression, and monitor treatment response |
title_full_unstemmed |
Transcriptomic biomarkers for tuberculosis: Validation of npc2 as a single mrna biomarker to diagnose tb, predict disease progression, and monitor treatment response |
title_sort |
Transcriptomic biomarkers for tuberculosis: Validation of npc2 as a single mrna biomarker to diagnose tb, predict disease progression, and monitor treatment response |
author |
Araujo, Leonardo S. de |
author_facet |
Araujo, Leonardo S. de Ribeiro-Alves, Marcelo Wipperman, Matthew F. Vorkas, Charles Kyriakos Pessler, Frank Saad, Maria Helena Féres |
author_role |
author |
author2 |
Ribeiro-Alves, Marcelo Wipperman, Matthew F. Vorkas, Charles Kyriakos Pessler, Frank Saad, Maria Helena Féres |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Araujo, Leonardo S. de Ribeiro-Alves, Marcelo Wipperman, Matthew F. Vorkas, Charles Kyriakos Pessler, Frank Saad, Maria Helena Féres |
dc.subject.en.pt_BR.fl_str_mv |
Mycobacterium tuberculosis NPC2 Niemann–Pick disease type C2 RNA Biomarkers Diagnosis mRNA Transcription Treatment Tuberculosis |
topic |
Mycobacterium tuberculosis NPC2 Niemann–Pick disease type C2 RNA Biomarkers Diagnosis mRNA Transcription Treatment Tuberculosis |
description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil / TWINCORE Centre for Experimental and Clinical Infection Research. Research Group Biomarkers for Infectious Diseases. Hannover, Germany. |
publishDate |
2021 |
dc.date.accessioned.fl_str_mv |
2021-12-09T22:14:22Z |
dc.date.available.fl_str_mv |
2021-12-09T22:14:22Z |
dc.date.issued.fl_str_mv |
2021 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
ARAUJO, Leonardo S. et al. Transcriptomic Biomarkers for Tuberculosis: Validation of NPC2 as a Single mRNA Biomarker to Diagnose TB, Predict Disease Progression, and Monitor Treatment Response. Cells vol. 10, n. 10, p. 1-18, 2021 |
dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/50271 |
dc.identifier.issn.pt_BR.fl_str_mv |
2073-4409 |
dc.identifier.doi.none.fl_str_mv |
10.3390/cells10102704 |
identifier_str_mv |
ARAUJO, Leonardo S. et al. Transcriptomic Biomarkers for Tuberculosis: Validation of NPC2 as a Single mRNA Biomarker to Diagnose TB, Predict Disease Progression, and Monitor Treatment Response. Cells vol. 10, n. 10, p. 1-18, 2021 2073-4409 10.3390/cells10102704 |
url |
https://www.arca.fiocruz.br/handle/icict/50271 |
dc.language.iso.fl_str_mv |
eng |
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eng |
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info:eu-repo/semantics/openAccess |
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openAccess |
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MDPI |
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MDPI |
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