Diacetylspermine is a novel prediagnostic serum biomarker for non-small-cell lung cancer and has additive performance with pro-surfactant protein B

William R. Wikoff, Samir Hanash, Brian DeFelice, Suzanne Miyamoto, Matt Barnett, Yang Zhao, Gary Goodman, Ziding Feng, David Gandara, Oliver Fiehn, Ayumu Taguchi

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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 N1,N12-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.

Original languageEnglish (US)
Pages (from-to)3880-3886
Number of pages7
JournalJournal of Clinical Oncology
Volume33
Issue number33
DOIs
StatePublished - Nov 20 2015

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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