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J Clin Oncol. 2015 Nov 20;33(33):3880-6. doi: 10.1200/JCO.2015.61.7779. Epub 2015 Aug 17.

Diacetylspermine Is a Novel Prediagnostic Serum Biomarker for Non-Small-Cell Lung Cancer and Has Additive Performance With Pro-Surfactant Protein B.

Author information

  • 1William R. Wikoff, Brian DeFelice, and Oliver Fiehn, National Institutes of Health West Coast Metabolomics Center, University of California, Davis, Davis; Suzanne Miyamoto and David Gandara, University of California, Davis, Davis Comprehensive Cancer Center, Sacramento, CA; Samir Hanash, Yang Zhao, Ziding Feng, and Ayumu Taguchi, The University of Texas MD Anderson Cancer Center, Houston, TX; and Matt Barnett and Gary Goodman, Fred Hutchison Cancer Research Center, Seattle, WA.
  • 2William R. Wikoff, Brian DeFelice, and Oliver Fiehn, National Institutes of Health West Coast Metabolomics Center, University of California, Davis, Davis; Suzanne Miyamoto and David Gandara, University of California, Davis, Davis Comprehensive Cancer Center, Sacramento, CA; Samir Hanash, Yang Zhao, Ziding Feng, and Ayumu Taguchi, The University of Texas MD Anderson Cancer Center, Houston, TX; and Matt Barnett and Gary Goodman, Fred Hutchison Cancer Research Center, Seattle, WA. ofiehn@ucdavis.edu.

Abstract

PURPOSE:

We have investigated the potential of metabolomics to discover blood-based biomarkers relevant to lung cancer screening and early detection. An untargeted metabolomics approach was applied to identify biomarker candidates using prediagnostic sera from the Beta-Carotene and Retinol Efficacy Trial (CARET) study.

PATIENTS AND METHODS:

A liquid chromatography/mass spectrometry hydrophilic interaction method designed to profile a wide range of metabolites was applied to prediagnostic serum samples from CARET participants (current or former heavy smokers), consisting of 100 patients who subsequently developed non-small-cell lung cancer (NSCLC) and 199 matched controls. A separate aliquot was used to quantify levels of pro-surfactant protein B (pro-SFTPB), a previously established protein biomarker for NSCLC. On the basis of the results from the discovery set, blinded validation of a metabolite, identified as N(1),N(12)-diacetylspermine (DAS), and pro-SFTPB was performed using an independent set of CARET prediagnostic sera from 108 patients with NSCLC and 216 matched controls.

RESULTS:

Serum DAS was elevated by 1.9-fold, demonstrating significant specificity and sensitivity in the discovery set for samples collected up to 6 months before diagnosis of NSCLC. In addition, DAS significantly complemented performance of pro-SFTPB in both the discovery and validations sets, with a combined area under the curve in the validation set of 0.808 (P < .001 v pro-SFTPB).

CONCLUSION:

DAS is a novel serum metabolite with significant performance in prediagnostic NSCLC and has additive performance with pro-SFTPB.

Comment in

PMID:
26282655
PMCID:
PMC4652011
DOI:
10.1200/JCO.2015.61.7779
[PubMed - indexed for MEDLINE]
Free PMC Article
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