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Metabolomic profiling for second primary lung cancer: A pilot case-control study.

Jacqueline V Aredo1, Natasha Purington2, Li Su3

  • 1Stanford University School of Medicine, Stanford, CA, USA.

Lung Cancer (Amsterdam, Netherlands)
|March 20, 2021
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Summary

Lung cancer survivors at high risk for a second primary lung cancer (SPLC) may have distinct serum metabolomic profiles. Metabolite biomarkers identified could aid in SPLC risk stratification and future screening strategies.

Keywords:
MetabolomicsRisk stratificationScreeningSecond primary lung cancerSurveillance

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Area of Science:

  • Oncology
  • Metabolomics
  • Biomarker Discovery

Background:

  • Lung cancer survivors face a significant risk of developing a second primary lung cancer (SPLC).
  • Current screening guidelines primarily address initial primary lung cancer (IPLC), lacking specific recommendations for SPLC.
  • Factors contributing to SPLC risk remain largely unestablished.

Purpose of the Study:

  • To investigate the potential of serum metabolomics for identifying metabolite biomarkers differentiating SPLC cases from IPLC controls.
  • To explore the utility of these biomarkers in a risk prediction model for SPLC.

Main Methods:

  • An untargeted metabolomics approach using ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) was applied to serum samples.
  • Serum samples from 82 SPLC cases and 82 matched IPLC controls were analyzed.
  • Random forest and logistic regression models identified SPLC-associated metabolites, which were integrated into a risk prediction model.

Main Results:

  • The analysis detected over 1000 named metabolites.
  • Significant SPLC-associated metabolites included 5-methylthioadenosine and phenylacetylglutamine, with approximately 1.5-fold increased levels in SPLC cases.
  • A risk prediction model incorporating metabolomic data showed a significantly higher proportion of SPLC cases in the highest risk quartile.

Conclusions:

  • SPLC cases exhibit distinct metabolomic profiles compared to non-SPLC patients.
  • Metabolomics-based risk stratification may assist in identifying individuals at higher risk for SPLC.
  • Further prospective studies are necessary to validate these findings for SPLC surveillance and screening.