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Investigation of metabolomic blood biomarkers for detection of adenocarcinoma lung cancer (training set)

ABSTRACT: Recently, the National Lung Cancer Screen Trial (NLST) demonstrated that low-dose CT (LDCT) screening could reduce mortality due to lung cancer by 20%. However, LDCT screening is largely hindered by high false-positive rates (96%), particularly in high-risk populations (heavy smokers), due to the low prevalence rates (less than 2%) of malignant tumors and high incidence of benign lung nodules. Consequently, complementary biomarkers that can be used in conjunction with LDCT screening to improve diagnostic capacities and reduce false-positive rates are highly desirable. Preferably, such complementary tools should be noninvasive and exhibit high sensitivity and specificity. The application of “-omic” sciences (genomics, transcriptomics, proteomics, and metabolomics) represents valuable tools for the discovery and validation of potential biomarkers that can be used for detection of NSCLC. Of these omic sciences, metabolomics has received considerable attention for its application in cancer. Metabolomics is the assessment of small molecules and biochemical intermediates (metabolites) using analytic instrumentation. Metabolites in blood are the product of all cellular processes, which are highly responsive to conditions of disease and environment, and represent the final output products of all organs forming a detailed systemic representation of an individual's current physiologic state. In this study, we used an untargeted metabolomics approach using gas chromatography time-of-flight mass spectrometry (GCTOFMS) to analyze the metabolome of serum and plasma samples both collected from the same patients that were organized into two independent case–control studies (ADC1 and ADC2). In both studies, only NSCLC adenocarcinoma was investigated. The overall objectives were to (i) determine whether individual or combinations of metabolites could be used as a diagnostic test to distinguish NSCLC adenocarcinoma from controls and (ii) to determine which, plasma or serum, provides more accurate classifiers for the detection of lung cancer. We developed individual and multimetabolite classifiers using a training test from the ADC1 study and evaluated the performance of the constructed classifiers, individually or in combination, in an independent test/validation study (ADC2). This study shows the potential of metabolite-based diagnostic tests for detection of lung adenocarcinoma. Further validation in a larger pool of samples is warranted.


TISSUE(S): Blood

DISEASE(S): Cancer

SUBMITTER: Oliver Fiehn  

PROVIDER: ST000385 | MetabolomicsWorkbench | Tue Oct 04 00:00:00 BST 2016

REPOSITORIES: MetabolomicsWorkbench

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