Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0026918 (
Mycobacterium
)
52,428
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:Transcriptomic Biomarkers for Tuberculosis: Evaluation of
DOCK9. EPHA4
, and
NPC2
mRNA Expression in Peripheral Blood. 2782 86