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Lipidomic profiling of colorectal lesions for real-time tissue recognition and risk-stratification using rapid evaporative ionisation mass spectrometry.

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Title: Lipidomic profiling of colorectal lesions for real-time tissue recognition and risk-stratification using rapid evaporative ionisation mass spectrometry.
Authors: Mason, SE
Manoli, E
Alexander, JL
Poynter, L
Ford, L
Paizs, P
Adebesin, A
McKenzie, JS
Rosini, F
Goldin, R
Darzi, A
Takats, Z
Kinross, JM
Item Type: Journal Article
Abstract: OBJECTIVE: Rapid Evaporative Ionisation Mass Spectrometry (REIMS) is a metabolomic technique analysing tissue metabolites, which can be applied intra-operatively in real-time. The objective of this study was to profile the lipid composition of colorectal tissues using REIMS, assessing its accuracy for real-time tissue recognition and risk-stratification. SUMMARY BACKGROUND DATA: Metabolic dysregulation is a hallmark feature of carcinogenesis, however it remains unknown if this can be leveraged for real-time clinical applications in colorectal disease. METHODS: Patients undergoing colorectal resection were included, with carcinoma, adenoma and paired-normal mucosa sampled. Ex vivo analysis with REIMS was conducted using monopolar diathermy, with the aerosol aspirated into a Xevo G2S QToF mass spectrometer. Negatively charged ions over 600-1000m/z were used for univariate and multivariate functions including linear discriminant analysis. RESULTS: 161 patients were included, generating 1013 spectra. Unique lipidomic profiles exist for each tissue type, with REIMS differentiating samples of carcinoma, adenoma and normal mucosa with 93 1% accuracy and 96 1% negative predictive value for carcinoma. Neoplasia (carcinoma or adenoma) could be predicted with 96 0% accuracy and 91 8% negative predictive value. Adenomas can be risk-stratified by grade of dysplasia with 93 5% accuracy, but not histological subtype. The structure of 61 lipid metabolites was identified, revealing that during colorectal carcinogenesis there is progressive increase in relative abundance of phosphatidylglycerols, sphingomyelins and mono-unsaturated fatty acid containing phospholipids. CONCLUSIONS: The colorectal lipidome can be sampled by REIMS and leveraged for accurate real-time tissue recognition, in addition to risk-stratification of colorectal adenomas. Unique lipidomic features associated with carcinogenesis are described.
Issue Date: 13-Aug-2021
Date of Acceptance: 1-Aug-2021
URI: http://hdl.handle.net/10044/1/91405
DOI: 10.1097/SLA.0000000000005164
ISSN: 0003-4932
Publisher: Lippincott, Williams & Wilkins
Journal / Book Title: Annals of Surgery
Volume: 00
Copyright Statement: © 2021 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Sponsor/Funder: Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Cancer Research UK
Society of American Gastrointestinal & Endoscopic Surgeons (SAGES)
Society of American Gastrointestinal & Endoscopic Surgeons (SAGES)
National Institute of Health Research
Funder's Grant Number: RD207
Keywords: 11 Medical and Health Sciences
Publication Status: Published online
Conference Place: United States
Online Publication Date: 2021-08-13
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Department of Surgery and Cancer
Faculty of Medicine
Institute of Global Health Innovation