Int J Biol Sci 2016; 12(2):246-256. doi:10.7150/ijbs.13805
A Group of Novel Serum Diagnostic Biomarkers for Multidrug-Resistant Tuberculosis by iTRAQ-2D LC-MS/MS and Solexa Sequencing
1. Institute of Cell Biology, Zhejiang University, Hangzhou 310058, P.R. China
The epidemic of pulmonary tuberculosis (TB), especially multidrug-resistance tuberculosis (MDR-TB) presented a major challenge for TB treatment today. We performed iTRAQ labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) and Solexa sequencing among MDR-TB patients, drug-sensitive tuberculosis (DS-TB) patients, and healthy controls. A total of 50 differentially expressed proteins and 43 differentially expressed miRNAs (fold change >1.50 or <0.60, P<0.05) were identified in the MDR-TB patients compared to both DS-TB patients and healthy controls. We found that 22.00% of differentially expressed proteins and 32.56% of differentially expressed miRNAs were related, and could construct a network mainly in complement and coagulation cascades. Significant differences in CD44 antigen (CD44), coagulation factor XI (F11), kininogen-1 (KNG1), miR-4433b-5p, miR-424-5p, and miR-199b-5p were found among MDR-TB patients, DS-TB patients and healthy controls (P<0.05) by enzyme-linked immunosorbent assay (ELISA) and SYBR green qRT-PCR validation. A strong negative correlation, consistent with the target gene prediction, was found between miR-199b-5p and KNG1 (r=-0.232, P=0.017). Moreover, we established the MDR-TB diagnostic model based on five biomarkers (CD44, KNG1, miR-4433b-5p, miR-424-5p, and miR-199b-5p). Our study proposes potential biomarkers for MDR-TB diagnosis, and also provides a new experimental basis to understand the pathogenesis of MDR-TB.
Keywords: multidrug-resistance tuberculosis, proteomic, transcriptomic, serum, biomarkers
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How to cite this article:
Wang C, Liu CM, Wei LL, Shi LY, Pan ZF, Mao LG, Wan XC, Ping ZP, Jiang TT, Chen ZL, Li ZJ, Li JC. A Group of Novel Serum Diagnostic Biomarkers for Multidrug-Resistant Tuberculosis by iTRAQ-2D LC-MS/MS and Solexa Sequencing. Int J Biol Sci 2016; 12(2):246-256. doi:10.7150/ijbs.13805. Available from http://www.ijbs.com/v12p0246.htm