Untargeted lipidomic features associated with colorectal cancer in a prospective cohort.

TitleUntargeted lipidomic features associated with colorectal cancer in a prospective cohort.
Publication TypeJournal Article
Year of Publication2018
AuthorsPerttula K, Schiffman C, Edmands WMB, Petrick L, Grigoryan H, Cai X, Gunter MJ, Naccarati A, Polidoro S, Dudoit S, Vineis P, Rappaport SM
JournalBMC Cancer
Volume18
Issue1
Pagination996
Date Published2018 Oct 19
ISSN1471-2407
Abstract

BACKGROUND: Epidemiologists are beginning to employ metabolomics and lipidomics with archived blood from incident cases and controls to discover causes of cancer. Although several such studies have focused on colorectal cancer (CRC), they all followed targeted or semi-targeted designs that limited their ability to find discriminating molecules and pathways related to the causes of CRC.

METHODS: Using an untargeted design, we measured lipophilic metabolites in prediagnostic serum from 66 CRC patients and 66 matched controls from the European Prospective Investigation into Cancer and Nutrition (Turin, Italy). Samples were analyzed by liquid chromatography-high-resolution mass spectrometry (LC-MS), resulting in 8690 features for statistical analysis.

RESULTS: Rather than the usual multiple-hypothesis-testing approach, we based variable selection on an ensemble of regression methods, which found nine features to be associated with case-control status. We then regressed each selected feature on time-to-diagnosis to determine whether the feature was likely to be either a potentially causal biomarker or a reactive product of disease progression (reverse causality).

CONCLUSIONS: Of the nine selected LC-MS features, four appear to be involved in CRC etiology and merit further investigation in prospective studies of CRC. Four other features appear to be related to progression of the disease (reverse causality), and may represent biomarkers of value for early detection of CRC.

DOI10.1186/s12885-018-4894-4
Alternate JournalBMC Cancer
PubMed ID30340609
PubMed Central IDPMC6194742
Grant ListP42 ES004705 / ES / NIEHS NIH HHS / United States
P42ES04705 / / National Institute for Environmental Health Sciences /
308610-FP7 / / European Commision /