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

Our plain-English summary of GC-MS-based untargeted metabolic profiling of malignant mesothelioma plasma, by D. Wang, J. Zhu, N. Li, et al (PeerJ, 2023).

The study

• Authors: D. Wang, J. Zhu, N. Li, H. Lu, Y. Gao, L. Zhuang, Z. Chen, W. Mao
• Journal: PeerJ
• Published: 2023;11:e15302
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

© 2023 Wang et al.

In plain English

This study, at Zhejiang Cancer Hospital in China, compared small chemical substances (metabolites) in blood plasma from 19 patients with confirmed malignant mesothelioma and 22 healthy people matched for age and sex. It used a laboratory method called gas chromatography-mass spectrometry. Patient samples were collected between March 2016 and March 2020, before any anti-cancer treatment. Thirteen patients had pleural and six had peritoneal mesothelioma, and seven of the 19 were recorded as asbestos-exposed. The authors identified 20 metabolites whose levels differed between the groups: 15 were higher and five were lower in patients. For five of these, a measure of how well they told patients apart from healthy controls (area under the curve) was above 0.9. Xanthurenic acid scored highest, at 0.969. Seven metabolic pathways showed statistically significant differences. The authors concluded that the findings offered potential treatment targets and diagnostic value. They called the work a pilot study because of its small size. They noted that some tests were not adjusted for multiple comparisons, which could produce false positives, and said a larger group is needed to confirm the results.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Untargeted plasma metabolomics study (gas chromatography-mass spectrometry) comparing mesothelioma patients with healthy controls; the authors call it a pilot study
• Who was studied: 19 patients with histopathologically confirmed malignant mesothelioma (13 pleural, 6 peritoneal) at Zhejiang Cancer Hospital, China, March 2016 to March 2020, none previously treated with anti-cancer therapy; and 22 age- and sex-matched healthy controls
• Exposure: The comparison was mesothelioma patients versus healthy controls, not an asbestos exposure. Asbestos exposure was recorded as yes for 7 of the 19 patients and no for 12. No fiber types, jobs or doses were reported.
• Main results:
  • 20 metabolites were annotated as differing between mesothelioma patients and healthy controls: 15 upregulated and 5 downregulated
  • Five metabolites had an area under the curve greater than 0.9 for distinguishing the mesothelioma group from the healthy control group
  • Xanthurenic acid had an area under the curve of 0.969
  • The other areas under the curve were: (s)-3,4-dihydroxybutyric acid 0.957, D-arabinose 0.922, gluconic acid 0.921, and beta-d-glucopyranuronic acid 0.923
  • 22 pathways were enriched for the differing metabolites, most related to amino acid metabolism; seven showed statistically significant differences (p less than 0.05)
  • Plasma histidine was significantly lower in the mesothelioma patients than in the healthy controls
  • Glyceric acid was significantly higher in the mesothelioma group than in the healthy control group
• The authors' conclusion: The authors concluded that the study found multiple dysregulated metabolic pathways in mesothelioma patients. In their view, these offered insight into the disease and potential therapeutic targets, and the diagnostic results showed a novel technique for diagnosis that needs further study with a larger sample.
• Limitations the authors state:
  • The sample size was small, so the authors consider the study only a pilot study
  • A larger cohort is required to validate the method
  • The chosen selection criteria (VIP greater than 1.5 and p less than 0.05) may have affected the results and may have excluded some valuable findings
  • Some hypothesis tests were not adjusted for multiple comparisons, which could lead to false positive results

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Asbestos Exposure, Biomarker.

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