title: A Group of Novel Serum Diagnostic Biomarkers for Multidrug-Resistant Tuberculosis by iTRAQ-2D LC-MS/MS and Solexa Sequencing.
abstract: 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.
authors.affiliation: 1. Institute of Cell Biology, Zhejiang University, Hangzhou 310058, P.R. China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: 1. Institute of Cell Biology, Zhejiang University, Hangzhou 310058, P.R. China.
authors.forename: Chang-Ming
authors.initials: CM
authors.lastname: Liu
authors.affiliation: 2. Department of Respiratory Medicine, The Sixth Hospital of Shaoxing, Shaoxing 312000, P.R. China.
authors.forename: Li-Liang
authors.initials: LL
authors.lastname: Wei
authors.affiliation: 3. Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou 310013, P.R. China.
authors.forename: Li-Ying
authors.initials: LY
authors.lastname: Shi
authors.affiliation: 4. Department of Tuberculosis, The First Hospital of Jiaxing, Jiaxing 314001, P.R. China.
authors.forename: Zhi-Fen
authors.initials: ZF
authors.lastname: Pan
authors.affiliation: 1. Institute of Cell Biology, Zhejiang University, Hangzhou 310058, P.R. China.
authors.forename: Lian-Gen
authors.initials: LG
authors.lastname: Mao
authors.affiliation: 3. Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou 310013, P.R. China.
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Wan
authors.affiliation: 1. Institute of Cell Biology, Zhejiang University, Hangzhou 310058, P.R. China.
authors.forename: Ze-Peng
authors.initials: ZP
authors.lastname: Ping
authors.affiliation: 1. Institute of Cell Biology, Zhejiang University, Hangzhou 310058, P.R. China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Jiang
authors.affiliation: 1. Institute of Cell Biology, Zhejiang University, Hangzhou 310058, P.R. China.
authors.forename: Zhong-Liang
authors.initials: ZL
authors.lastname: Chen
authors.affiliation: 1. Institute of Cell Biology, Zhejiang University, Hangzhou 310058, P.R. China.
authors.forename: Zhong-Jie
authors.initials: ZJ
authors.lastname: Li
authors.affiliation: 1. Institute of Cell Biology, Zhejiang University, Hangzhou 310058, P.R. China.
authors.forename: Ji-Cheng
authors.initials: JC
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid; D057225:Data Mining; D003663:Decision Trees; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood; D008875:Middle Aged; D040901:Proteomics; D012372:ROC Curve; D017421:Sequence Analysis / Q000379:methods; D053719:Tandem Mass Spectrometry; D059467:Transcriptome; D018088:Tuberculosis, Multidrug-Resistant / Q000097:blood / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: biomarkers; multidrug-resistance tuberculosis; proteomic; serum; transcriptomic