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

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.

• Authors: William R Wikoff, Samir Hanash, Brian DeFelice, Suzanne Miyamoto, Matt Barnett, Yang Zhao, Gary Goodman, Ziding Feng, David Gandara, Oliver Fiehn, Ayumu Taguchi
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 33 Issue 33 Pg. 3880-6 (Nov 20 2015) ISSN: 1527-7755 [Electronic] United States
• PMID: 26282655 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2015 by American Society of Clinical Oncology.

Chemical References

• Biomarkers, Tumor
• Protein Precursors
• Pulmonary Surfactant-Associated Proteins
• SFTPB protein, human
• Spermine
• N',N''-diacetylspermine

Topics

• Aged
• Biomarkers, Tumor (blood)
• Carcinoma, Non-Small-Cell Lung (blood, epidemiology, physiopathology)
• Case-Control Studies
• Chromatography, Liquid (methods)
• Disease-Free Survival
• Early Detection of Cancer (methods)
• Female
• Humans
• Lung Neoplasms (blood, epidemiology, physiopathology)
• Male
• Mass Spectrometry (methods)
• Middle Aged
• Prognosis
• Protein Precursors (blood)
• Pulmonary Surfactant-Associated Proteins (blood)
• ROC Curve
• Risk Assessment
• Sensitivity and Specificity
• Smoking (adverse effects, blood)
• Spermine (analogs & derivatives, blood)
• Statistics, Nonparametric
• Survival Analysis