GC-MS-based untargeted metabolic profiling of malignant mesothelioma plasma

PeerJ. 2023 May 18:11:e15302. doi: 10.7717/peerj.15302. eCollection 2023.

Abstract

Background: Malignant mesothelioma (MM) is a cancer caused mainly by asbestos exposure, and is aggressive and incurable. This study aimed to identify differential metabolites and metabolic pathways involved in the pathogenesis and diagnosis of malignant mesothelioma.

Methods: By using gas chromatography-mass spectrometry (GC-MS), this study examined the plasma metabolic profile of human malignant mesothelioma. We performed univariate and multivariate analyses and pathway analyses to identify differential metabolites, enriched metabolism pathways, and potential metabolic targets. The area under the receiver-operating curve (AUC) criterion was used to identify possible plasma biomarkers.

Results: Using samples from MM (n = 19) and healthy control (n = 22) participants, 20 metabolites were annotated. Seven metabolic pathways were disrupted, involving alanine, aspartate, and glutamate metabolism; glyoxylate and dicarboxylate metabolism; arginine and proline metabolism; butanoate and histidine metabolism; beta-alanine metabolism; and pentose phosphate metabolic pathway. The AUC was used to identify potential plasma biomarkers. Using a threshold of AUC = 0.9, five metabolites were identified, including xanthurenic acid, (s)-3,4-hydroxybutyric acid, D-arabinose, gluconic acid, and beta-d-glucopyranuronic acid.

Conclusions: To the best of our knowledge, this is the first report of a plasma metabolomics analysis using GC-MS analyses of Asian MM patients. Our identification of these metabolic abnormalities is critical for identifying plasma biomarkers in patients with MM. However, additional research using a larger population is needed to validate our findings.

Keywords: Biomarker; GC-MS; Malignant mesothelioma; Metabolomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression
  • Alanine
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Mesothelioma, Malignant*
  • Metabolomics

Substances

  • Alanine

Grants and funding

This work was supported by the National Natural Science Foundation of China (81672315); Key R&D Program Projects in Zhejiang Province (2018C04009); Medical and the Health Science Project of Zhejiang Province (2022KY622); and the Zhejiang Provincial Natural Science Foundation of China (LY23H010002). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.