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

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Abstract

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.

The plasma pseudotargeted metabolic profiling suggested the metabolic alterations in bladder cancer (BC) and the significantly differential metabolites for BC discrimination

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Acknowledgments

The study has been supported by the foundations (No. 21435006, No. 21375127) and the creative research group project (No. 21321064) from the National Natural Science Foundation of China.

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    Authors and Affiliations

    1. Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian, Liaoning, 116023, China

      Yang Zhou, Xin Lu, Zhongda Zeng, Chunxiu Hu, Xinyu Liu, Yanli Li & Guowang Xu

    2. University of Chinese Academy of Sciences, Beijing, 100049, China

      Yang Zhou & Xinyu Liu

    3. Department of Urology, Shanghai Changhai Hospital, Secondary Military Medical University, Shanghai, 200433, China

      Ruixiang Song, Zhensheng Zhang, Jianguo Hou, Yinghao Sun & Chuanliang Xu

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    1. Yang Zhou
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    Correspondence to Xin Lu or Chuanliang Xu.

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    Yang Zhou and Ruixiang Song contributed equally to this work.

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    Zhou, Y., Song, R., Zhang, Z. et al. The development of plasma pseudotargeted GC-MS metabolic profiling and its application in bladder cancer. Anal Bioanal Chem 408, 6741–6749 (2016). https://doi.org/10.1007/s00216-016-9797-0

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