The development of plasma pseudotargeted GC-MS metabolic profiling and its application in bladder cancer

被引:47
作者
Zhou, Yang [1 ,2 ]
Song, Ruixiang [3 ]
Zhang, Zhensheng [3 ]
Lu, Xin [1 ]
Zeng, Zhongda [1 ]
Hu, Chunxiu [1 ]
Liu, Xinyu [1 ,2 ]
Li, Yanli [1 ]
Hou, Jianguo [3 ]
Sun, Yinghao [3 ]
Xu, Chuanliang [3 ]
Xu, Guowang [1 ]
机构
[1] Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, 457 Zhongshan Rd, Dalian 116023, Liaoning, Peoples R China
[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
[3] Secondary Mil Med Univ, Shanghai Changhai Hosp, Dept Urol, Shanghai 200433, Peoples R China
基金
中国国家自然科学基金;
关键词
Metabolomics; Bladder cancer; Metabolic profiling; Gas chromatography-mass spectrometry; Pseudotargeted; Plasma; GAS CHROMATOGRAPHY/MASS SPECTROMETRY; PENTOSE-PHOSPHATE PATHWAY; MASS SPECTROMETRY; TOBACCO-LEAVES; EXPRESSION; URINARY; SURVIVAL; REVEALS;
D O I
10.1007/s00216-016-9797-0
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Bladder cancer (BC) is a fatal malignancy with considerable mortality. BC urinary metabolomics has been extensively investigated for biomarker discovery, but few BC blood metabolomic studies have been performed. Hence, a plasma pseudotargeted metabolomic method based on gas chromatography-mass spectrometry with selected ion monitoring (GC-MS-SIM) was developed to study metabolic alterations in BC. The analytical performance of the developed method was compared with that of a nontargeted method. The relative standard deviation (RSD) values of 89 and 70.7 % of the peaks obtained using the pseudotargeted and nontargeted methods, respectively, were less than 20 %. The Pearson correlations of 90.7 and 78.3 % of the peaks obtained using the pseudotargeted and nontargeted methods, respectively, exceeded 0.90 in the linearity evaluation. Compared with the nontargeted method, the signal-to-noise ratios (S/N) of 97.9 and 69.3 % of the peaks increased two- and fivefold, respectively. The developed method was fully validated, with good precision, recovery, and stability of the trimethylsilyl (TMS) derivatives. The method was applied to investigate BC. Significant increases in the contents of metabolites involved in, for example, the pentose phosphate pathway (PPP) and nucleotide and fatty acid synthesis were found in the high-grade (HG) BC group compared to the healthy control (HC) group. These differences imply that the activated PPP may regulate BC cell proliferation by promoting lipid and nucleotide biosynthesis and the detoxification of reactive oxygen species (ROS). These results illustrate that the plasma pseudotargeted method is a powerful tool for metabolic profiling.
引用
收藏
页码:6741 / 6749
页数:9
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