Screening and identification of four serum miRNAs as novel potential biomarkers for cured pulmonary tuberculosis

Rapid a nd efficient methods for the determination of cured pulmonary tuberculosis (TB) are lacking. We screened serum miRNAs using the Solexa sequencing method among untreated TB patients, two-month treated TB patients, cured TB patients, and healthy controls. A total of 100 differentially expressed miRNAs were identified in cured TB patients, including 37 up-regulated (fold change > 1.50, P < 0.05) and 63 down-regulated (fold change < 0.60, P < 0.05) miRNAs. Gene ontology (GO) enrichment analysis revealed that most of the predicted genes were present in the nucleus with a strong protein binding function. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis strongly suggested alterations in the metabolic pathways. Following quantitative real time chain reaction (qRT-PCR), significantly reduced expression levels of miR-21-5p (0.30, P < 0.001), miR-92a-3p (0.63, P < 0.001), and miR148b-3p (0.17, P < 0.001) were found in the cured TB patients compared with the untreated TB patients, while significantly increased expression levels of miR-21-5p (2.09, P = 0.001), miR-92a-3p (1.40, P = 0.005), and miR-148b-3p (4.80, P = 0.003) were found in the untreated TB patients compared with the healthy controls. And significantly increased level of miR-125a-5p was found between two-month treated TB patients and untreated TB patients (1.81, P = 0.004). We established a cured TB model with 83.96% accuracy by four miRNAs (miR-21-5p, miR-92a-3p, miR-148b-3p, and miR-125a-5p), and also established a diagnostic model with 70.09% accuracy. Our study provides experimental data for establishing objective indicators of cured TB, and also provides a new experimental basis to understand the pathogenesis and prognosis of TB. (C) 2017 Elsevier Ltd. All rights reserved.