Transcriptomic Biomarkers for Tuberculosis: Validation of as a Single mRNA Biomarker to Diagnose TB, Predict Disease Progression, and Monitor Treatment Response.
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Authors
de Araujo, Leonardo SRibeiro-Alves, Marcelo
Wipperman, Matthew F
Vorkas, Charles Kyriakos
Pessler, Frank
Saad, Maria Helena Féres
Issue Date
2021-10-09
Metadata
Show full item recordAbstract
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.Citation
Cells. 2021 Oct 9;10(10):2704. doi: 10.3390/cells10102704.Affiliation
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.Publisher
MDPIJournal
CellsPubMed ID
34685683Type
ArticleLanguage
enEISSN
2073-4409ae974a485f413a2113503eed53cd6c53
10.3390/cells10102704
Scopus Count
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- Creative Commons