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 R Gandara, Oliver Fiehn, Ayumu Taguchi

Research output: Contribution to journalArticle

42 Citations (Scopus)

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

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Surface-Active Agents
Non-Small Cell Lung Carcinoma
Biomarkers
Vitamin A
Serum
Metabolomics
Carotenoids
beta Carotene
Hydrophobic and Hydrophilic Interactions
Early Detection of Cancer
Liquid Chromatography
Area Under Curve
Lung Neoplasms
Mass Spectrometry
N',N''-diacetylspermine
IgA receptor
Sensitivity and Specificity
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Diacetylspermine is a novel prediagnostic serum biomarker for non-small-cell lung cancer and has additive performance with pro-surfactant protein B. / Wikoff, William R.; Hanash, Samir; DeFelice, Brian; Miyamoto, Suzanne; Barnett, Matt; Zhao, Yang; Goodman, Gary; Feng, Ziding; Gandara, David R; Fiehn, Oliver; Taguchi, Ayumu.

In: Journal of Clinical Oncology, Vol. 33, No. 33, 20.11.2015, p. 3880-3886.

Research output: Contribution to journalArticle

Wikoff, WR, Hanash, S, DeFelice, B, Miyamoto, S, Barnett, M, Zhao, Y, Goodman, G, Feng, Z, Gandara, DR, Fiehn, O & Taguchi, A 2015, 'Diacetylspermine is a novel prediagnostic serum biomarker for non-small-cell lung cancer and has additive performance with pro-surfactant protein B', Journal of Clinical Oncology, vol. 33, no. 33, pp. 3880-3886. https://doi.org/10.1200/JCO.2015.61.7779
Wikoff, William R. ; Hanash, Samir ; DeFelice, Brian ; Miyamoto, Suzanne ; Barnett, Matt ; Zhao, Yang ; Goodman, Gary ; Feng, Ziding ; Gandara, David R ; Fiehn, Oliver ; Taguchi, Ayumu. / Diacetylspermine is a novel prediagnostic serum biomarker for non-small-cell lung cancer and has additive performance with pro-surfactant protein B. In: Journal of Clinical Oncology. 2015 ; Vol. 33, No. 33. pp. 3880-3886.
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AU - Wikoff, William R.

AU - Hanash, Samir

AU - DeFelice, Brian

AU - Miyamoto, Suzanne

AU - Barnett, Matt

AU - Zhao, Yang

AU - Goodman, Gary

AU - Feng, Ziding

AU - Gandara, David R

AU - Fiehn, Oliver

AU - Taguchi, Ayumu

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N2 - 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.

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