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 RDB04 25165 n/a WSSS_P67267 |
Keywords: | 11 Medical and Health Sciences Surgery |
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 |