Assessment of plasma amino acids, purines, tricarboxylic acid cycle metabolites, and lipids levels in NSCLC patients based on LC-MS/MS quantification

J Pharm Biomed Anal. 2022 Nov 30:221:114990. doi: 10.1016/j.jpba.2022.114990. Epub 2022 Aug 8.

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of malignant tumor of the lung with poor prognosis. Currently, there is still no effective strategy for diagnosing lung cancer from the perspective of multiple biomarkers containing both polar and nonpolar molecules. In order to explore the pathological changes of NSCLC at the endogenous molecule levels, and further establish the strategy for identifying and monitoring drug efficacy of NSCLC, targeted metabolomics and lipidomics studies were established with NSCLC patients. Polar metabolites including 21 amino acids, 7 purines, 6 tricarboxylic acid (TCA) cycle metabolites, and nonpolar lipids like phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), sphingomyelin (SM), and ceramide (Cer), diacylglycerol (DG), triacylglycerol (TG), were quantitatively determined based on LC-MS/MS, taking into account their metabolism were significantly concerned with the occurrence of lung cancer in previous study. As a result, 14 polar metabolites and 16 lipids were prominently altered in the plasma of NSCLC patients, among which, after multivariate statistical analysis, LPC 18:0 (sn-2), L-Phenylalanine (Phe), oxaloacetic acid (OAA) and xanthine (XA) were screened out as potential small molecules and lipid biomarkers for NSCLC. Furthermore, a new strategy for formulating equation of NSCLC identification was proposed and clinical utility was successfully evaluated through Kangai injection treatment to NSCLC patients. Taking together, this study investigated the pathological changes of NSCLC from the perspective of endogenous polar and nonpolar molecules, and shed a light on identification of NSCLC.

Keywords: Biomarker; Lipidomics; Metabolomics; Non-small cell lung cancer; Pathological changes.

MeSH terms

  • Amino Acids
  • Biomarkers
  • Carcinoma, Non-Small-Cell Lung*
  • Ceramides
  • Chromatography, Liquid
  • Citric Acid Cycle
  • Diglycerides
  • Humans
  • Lung Neoplasms*
  • Lysophosphatidylcholines
  • Oxaloacetates
  • Phenylalanine
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • Purines
  • Sphingomyelins
  • Tandem Mass Spectrometry
  • Tricarboxylic Acids
  • Triglycerides
  • Xanthines

Substances

  • Amino Acids
  • Biomarkers
  • Ceramides
  • Diglycerides
  • Lysophosphatidylcholines
  • Oxaloacetates
  • Phosphatidylcholines
  • Phosphatidylethanolamines
  • Purines
  • Sphingomyelins
  • Tricarboxylic Acids
  • Triglycerides
  • Xanthines
  • Phenylalanine