Mass spectrometry-based identification of new serum biomarkers in patients with multidrug resistant pulmonary tuberculosis.
10.12122/j.issn.1673-4254.2019.12.04
- Author:
Dongzi LIN
1
;
Wei WANG
1
;
Feng QIU
2
;
Yumei LI
3
;
Xiaolin YU
3
;
Bingyao LIN
1
;
Yinwen CHEN
3
;
Chunyan LEI
1
;
Yan MA
1
;
Jincheng ZENG
4
;
Jie ZHOU
1
Author Information
1. Department of Laboratory Medicine, Foshan Forth People's Hospital, Foshan 528041, China.
2. Department of Laboratory Medicine, Nanhai Hospital, Southern Medical University, Foshan 528244, China.
3. Department of Laboratory Medicine, Dongguan Sixth People's Hospital, Dongguan 523008, China.
4. Dongguan Key Laboratory of Medical Bioactive Molecular Developmental and Translational Research, Guangdong Medical University, Dongguan 523808, China.
- Publication Type:Journal Article
- Keywords:
LC-MS/MS;
drug resistance;
metabolic markers;
pulmonary tuberculosis;
serum
- MeSH:
Biomarkers;
Chromatography, Liquid;
Humans;
Tandem Mass Spectrometry;
Tuberculosis, Multidrug-Resistant;
Tuberculosis, Pulmonary
- From:
Journal of Southern Medical University
2019;39(12):1409-1420
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To screen new serum metabolic biomarkers for different drug resistance profiles of pulmonary tuberculosis (TB) and explore their mechanisms and functions.
METHODS:We collected serum samples from TB patients with drug sensitivity (DS), monoresistance to isoniazid (MR-INH), monoresistance to rifampin (MR-RFP), multidrug resistance (MDR), and polyresistance (PR). The metabolites in the serum samples were extracted by oscillatory and deproteinization for LC-MS/MS analysis, and the results were normalized by Pareto-scaling method and analyzed using Metaboanalyst 4.0 software to identify the differential metabolites. The differential metabolites were characterized by function enrichment and co-expression analysis to explore their function and possible pathological mechanisms.
RESULTS:Compared with the DS group, 286 abnormally expressed metabolites were identified in MR-INH group, 362 in MR-RPF group, 277 in MDR group and 1208 in PR group by LC-MS/MS analysis. Acetylagmatine ( < 0.05), aminopentol ( < 0.05), and tetracosanyl oleate ( < 0.05) in MR-INH group; Ala His Pro Thr ( < 0.001) and glycinoprenol-9 ( < 0.05) in MR-RFP group; trimethylamine ( < 0.05), penaresidin A ( < 0.05), and verazine ( < 0.05) in MDR group; and PIP (18:1(11Z)/ 18:3(6Z, 9Z, 12Z)) ( < 0.001), Pro Arg Trp Tyr ( < 0.001), N-methyldioctylamine ( < 0.001), and phytolaccoside E ( < 0.05) in PR group all showed significant differential expressions. Significant differential expressions of phthalic acid mono-2-ethylhexyl ester ( < 0.05) and eicosanoyl-EA ( < 0.05) were found in all the drug resistant groups as compared with DS group.
CONCLUSIONS:Acetylagmatine, aminopentol, tetracosanyl oleate, Ala His Pro Thr, glycinoprenol-9, trimethylamine, penaresidin A, verazine, PIP(18:1(11Z)/18:3(6Z, 9Z, 12Z)), Pro Arg Trp Tyr, N-methyldioctylamine, phytolaccoside E, phthalic acid mono-2-ethylhexyl ester, and eicosanoyl-EA are potentially new biomarkers that indicate monoresistance, multi-drug resistance and polyresistance of Mycobacterium tuberculosis. The combined use of these biomarkers potentially allows for assessment of drug resistance in TB and enhances the diagnostic sensitivity and specificity.
