2. Academic Validation
  3. Targeted profiling of polar metabolites in cancer metabolic reprogramming by hydrophilic interaction liquid chromatography-tandem mass spectrometry

Targeted profiling of polar metabolites in cancer metabolic reprogramming by hydrophilic interaction liquid chromatography-tandem mass spectrometry

  • J Chromatogr A. 2022 Dec 20:1686:463654. doi: 10.1016/j.chroma.2022.463654.
Xue-Man Dong 1,  Pu Wu 2,  Long-Hui Cheng 2,  Lan Shou 3,  Heng Dong 2,  Xiao-Yu Chen 2,  Hao-Jin Gao 2,  Jian-Xiang Chen 2,  Fei Xiang 4,  Qi Zhang 5,  Da-Hong Zhang 5,  Jian-Liang Zhou 6,  Tian Xie 7
Affiliations

Affiliations

  • 1 Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China.
  • 2 School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China.
  • 3 Medical Center, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, China.
  • 4 Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China. Electronic address: xiangfei1988@zju.edu.cn.
  • 5 Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital, Hangzhou 310014, China.
  • 6 School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China. Electronic address: cpuzhou@163.com.
  • 7 Innovation Research Institute of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou 311121, China. Electronic address: xbs@hznu.edu.cn.
PMID: 36434830 DOI: 10.1016/j.chroma.2022.463654
Abstract

Metabolic reprogramming of Cancer cells is a hallmark of Cancer, in which the polar metabolites involving aerobic glycolysis, pentose phosphate pathway (PPP), tricarboxylic acid (TCA) cycle, and glutaminolysis play a crucial role in the occurrence and development of Cancer. Therefore, targeted analysis of the polar metabolites in these pathways is of great value for understanding cancers, finding diagnostic biomarkers, and identifying therapeutic targets. However, it is still challenging to directly determine polar metabolites in these pathways without derivatization due to their diverse chemical properties, isomers, and strong polarity. Herein, a highly selective and sensitive HILIC-MS/MS method was developed for direct determination of the polar metabolites in aerobic glycolysis, PPP, TCA cycle, and glutaminolysis pathways. Without derivatization, 19 polar metabolites and their isomers with carbonyl, carboxyl, or phosphoryl groups in human plasma and cell extracts of prostate Cancer (PC) were determined with strong retention and high resolution. This method has been widely verified by measuring linearity, precision, sensitivity, repeatability, matrix effect, and accuracy. The analysis of plasma samples by HILIC-MS/MS revealed distinct PC-specific metabolic signatures compared to a healthy control. In addition, this method could also be used to screen the targets of metabolic inhibitors at the cellular level. We conclude that the developed HILIC-MS/MS method provides a valuable means to study the Cancer metabolic reprogramming or energy metabolism in living organisms.

Keywords

Cancer metabolic reprogramming; HILIC-MS/MS; Human plasma; Polar metabolites; Prostate cancer.

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