Prediction of platinum-based chemotherapy efficacy in lung cancer based on LC-MS metabolomics approach

J Pharm Biomed Anal. 2018 May 30:154:95-101. doi: 10.1016/j.jpba.2018.02.051. Epub 2018 Feb 23.

Abstract

Lung cancer is the common cause of cancer-related death worldwide. Platinum-based chemotherapy is the cornerstone of treatment for lung cancer. Platinum sensitivity is a major possibility for effective cancer treatment. In this study, several potential biomarkers were identified for evaluating and predicting the response to platinum-based chemotherapy. LC-MS-based metabolomics was performed on plasma samples from 43 lung cancer patients with different chemotherapy efficacy. By combing multivariate statistical analysis, pathway analysis with correlation analysis, 8 potential biomarkers were significantly associated with platinum chemotherapy response. Moreover, a prediction model with these biomarkers involved in citric acid cycle, glutamate metabolism and amino acid metabolism, showed 100% sensitivity and 100% specificity for predicting chemotherapy response in a validation set. Interestingly, 2-hydroxyglutaric acid (2-HG) as an oncometabolite accumulated in lung cancer was remarkably elevated in the partial response (PR) patients. Collectively, our findings implicated that metabolomics can serve as a potential tool to select lung cancer patients that are more likely to benefit from the platinum-based treatment.

Keywords: Biomarker; Chemotherapy efficacy; LC–MS; Lung cancer; Metabolomics; Platinum.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Chromatography, High Pressure Liquid / instrumentation
  • Chromatography, High Pressure Liquid / methods
  • Female
  • Glutarates / analysis
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Male
  • Metabolic Networks and Pathways
  • Metabolomics / methods*
  • Middle Aged
  • Models, Biological
  • Patient Selection
  • Platinum Compounds / therapeutic use*
  • Tandem Mass Spectrometry / instrumentation
  • Tandem Mass Spectrometry / methods
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Glutarates
  • Platinum Compounds
  • alpha-hydroxyglutarate