Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620679
Title:
Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood.
Authors:
de Araujo, Leonardo S; Vaas, Lea A I; Ribeiro-Alves, Marcelo; Geffers, Robert; Mello, Fernanda C Q; de Almeida, Alexandre S; Moreira, Adriana da S R; Kritski, Afrânio L; Lapa E Silva, José R; Moraes, Milton O; Pessler, Frank; Saad, Maria H F
Abstract:
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.
Affiliation:
Twincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany.
Citation:
Transcriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood. 2016, 7:1586 Front Microbiol
Journal:
Frontiers in microbiology
Issue Date:
2016
URI:
http://hdl.handle.net/10033/620679
DOI:
10.3389/fmicb.2016.01586
PubMed ID:
27826286
Type:
Article
Language:
en
Appears in Collections:
publications of the research group biomarker in infection and immunity [[TC] BIOM)

Full metadata record

DC FieldValue Language
dc.contributor.authorde Araujo, Leonardo Sen
dc.contributor.authorVaas, Lea A Ien
dc.contributor.authorRibeiro-Alves, Marceloen
dc.contributor.authorGeffers, Roberten
dc.contributor.authorMello, Fernanda C Qen
dc.contributor.authorde Almeida, Alexandre Sen
dc.contributor.authorMoreira, Adriana da S Ren
dc.contributor.authorKritski, Afrânio Len
dc.contributor.authorLapa E Silva, José Ren
dc.contributor.authorMoraes, Milton Oen
dc.contributor.authorPessler, Franken
dc.contributor.authorSaad, Maria H Fen
dc.date.accessioned2017-01-05T10:48:04Z-
dc.date.available2017-01-05T10:48:04Z-
dc.date.issued2016-
dc.identifier.citationTranscriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood. 2016, 7:1586 Front Microbiolen
dc.identifier.pmid27826286-
dc.identifier.doi10.3389/fmicb.2016.01586-
dc.identifier.urihttp://hdl.handle.net/10033/620679-
dc.description.abstractLately, 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleTranscriptomic Biomarkers for Tuberculosis: Evaluation of DOCK9. EPHA4, and NPC2 mRNA Expression in Peripheral Blood.en
dc.typeArticleen
dc.contributor.departmentTwincore Centre of Experimental and Clinical Infection Research; a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover 30625, Germany.en
dc.identifier.journalFrontiers in microbiologyen

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