Transcriptomic biomarkers for tuberculosis: Validation of npc2 as a single mrna biomarker to diagnose tb, predict disease progression, and monitor treatment response

Detalhes bibliográficos
Autor(a) principal: Araujo, Leonardo S. de
Data de Publicação: 2021
Outros Autores: Ribeiro-Alves, Marcelo, Wipperman, Matthew F., Vorkas, Charles Kyriakos, Pessler, Frank, Saad, Maria Helena Féres
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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spelling 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&nbsp;p < 0.01, DOCK9low&nbsp;p < 0.01, and EPHA4low&nbsp;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 19:14:22.898oai:www.arca.fiocruz.br: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ório 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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
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/50271/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/50271/2/Transcriptomic_Marcelo_Alves_etal_INI_2021.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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