Untargeted lipidomic features associated with colorectal cancer in a prospective cohort
Author(s)
Type
Journal Article
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.
Date Issued
2018-10-19
Online Publication Date
2018-10-19
2018-11-16T15:57:51Z
Date Acceptance
2018-10-03
ISSN
1471-2407
Publisher
BioMed Central
Journal / Book Title
BMC Cancer
Volume
18
Issue
1
Copyright Statement
© 2018 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000447737100002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Oncology
Colorectal cancer
Lipidomics
Metabolomics
EPIC
Untargeted
Biomarkers
MASS-SPECTROMETRY DATA
CHAIN FATTY-ACIDS
COLON-CANCER
METABOLITE IDENTIFICATION
LIQUID-CHROMATOGRAPHY
DATA SETS
RISK
NUTRITION
SERUM
MEAT
1112 Oncology And Carcinogenesis
Oncology & Carcinogenesis
Publication Status
Published
Article Number
996
Date Publish Online
2018-10-19