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A group of novel serum diagnostic biomarkers for multidrug‐resistant tuberculosis by iTRAQ‐2D LC‐MS/MS and Solexa sequencing
Author(s) -
WANG CHONG,
LIU CHANGMING,
WEI LILIANG,
SHI LIYING,
PAN ZHIFEN,
MAO LIANGEN,
WAN XIAOCHEN,
PING ZEPENG,
JIANG TINGTING,
CHEN ZHONGLIANG,
LI ZHONGJIE,
LI JICHENG
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.601.3
Subject(s) - tuberculosis , medicine , multiple drug resistance , fold change , drug resistance , immunology , biology , gene , pathology , microbiology and biotechnology , gene expression , biochemistry
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 KNG1 and miR‐199b‐5p (r=−0.232, P =0.017). Moreover, we established a diagnostic model for MDR‐TB patients and healthy controls with a sensitivity of 100.00% and a specificity of 88.33% (overall accuracy 93.14%), and also established a diagnostic model for MDR‐TB patients and DS‐TB patients with a sensitivity of 83.33% and a specificity of 88.33% (overall accuracy 86.27%). Our study proposes potential biomarkers for MDR‐TB diagnosis, and also provides a new experimental basis to understand the pathogenesis of MDR‐TB. Support or Funding Information This work was supported by grants from the National Natural Science Foundation of China (No.81573709, No.81273882), the National Basic Research Program of China (No.2014CB543002) and the National Special Sci‐Tech Projects (No.2012ZX10005001‐006).