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

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.