William R Wikoff1, Samir Hanash1, Brian DeFelice1, Suzanne Miyamoto1, Matt Barnett1, Yang Zhao1, Gary Goodman1, Ziding Feng1, David Gandara1, Oliver Fiehn2, Ayumu Taguchi1. 1. William R. Wikoff, Brian DeFelice, and Oliver Fiehn, National Institutes of Health West Coast Metabolomics Center, University of California, Davis, Davis; Suzanne Miyamoto and David Gandara, University of California, Davis, Davis Comprehensive Cancer Center, Sacramento, CA; Samir Hanash, Yang Zhao, Ziding Feng, and Ayumu Taguchi, The University of Texas MD Anderson Cancer Center, Houston, TX; and Matt Barnett and Gary Goodman, Fred Hutchison Cancer Research Center, Seattle, WA. 2. William R. Wikoff, Brian DeFelice, and Oliver Fiehn, National Institutes of Health West Coast Metabolomics Center, University of California, Davis, Davis; Suzanne Miyamoto and David Gandara, University of California, Davis, Davis Comprehensive Cancer Center, Sacramento, CA; Samir Hanash, Yang Zhao, Ziding Feng, and Ayumu Taguchi, The University of Texas MD Anderson Cancer Center, Houston, TX; and Matt Barnett and Gary Goodman, Fred Hutchison Cancer Research Center, Seattle, WA. ofiehn@ucdavis.edu.
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.
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.
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