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

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

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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Biomarkers, Tumor / blood*
  • Carcinoma, Non-Small-Cell Lung / blood*
  • Carcinoma, Non-Small-Cell Lung / epidemiology
  • Carcinoma, Non-Small-Cell Lung / physiopathology
  • Case-Control Studies
  • Chromatography, Liquid / methods
  • Disease-Free Survival
  • Early Detection of Cancer / methods*
  • Female
  • Humans
  • Lung Neoplasms / blood*
  • Lung Neoplasms / epidemiology
  • Lung Neoplasms / 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
  • Smoking / blood
  • Spermine / analogs & derivatives*
  • Spermine / blood
  • Statistics, Nonparametric
  • Survival Analysis

Substances

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