Diacetylspermine Is a Novel Prediagnostic Serum Biomarker for Non–Small-Cell Lung Cancer and Has Additive Performance With Pro-Surfactant Protein B
Mené à partir d'échantillons sériques prélevés sur 100 patients fumeurs ou anciens fumeurs atteints d'un cancer du poumon non à petites cellules et sur 199 témoins, puis validé sur 108 autres patients et sur 216 témoins, cet essai montre que le dosage de la diacétylspermine permet de détecter précocement un cancer du poumon non à petites cellules et peut, en combinaison avec le dosage de la protéine B du surfactant pulmonaire, améliorer le diagnostic de la maladie
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.
Journal of Clinical Oncology , résumé, 2015