Abstract 4536: Rapid evaporative ionization mass spectrometry (REIMS) analysis of the mucosal lipidome has a high diagnostic accuracy for adenomas and early colorectal cancer

Abstract

Abstract Introduction The aim of this study was to determine the diagnostic accuracy of REIMS for dysplasia in human adenomas and early colorectal cancer and to determine changes in mucosal lipid chemistry during cancer initiation. Moreover, we attempted to develop a proof of concept first in man study of a novel REIMS-based endoscope for in-vivo chemical phenotyping of adenomas based on the real time analysis of phosphatidic acid (PA) and phosphatidylethanolamine (PE) metabolism. Experimental procedure A prospective, observational cross-sectional cohort study was performed in patients undergoing elective resection for colorectal cancer or colonoscopy at Imperial College London NHS Trust. Two tissue types were obtained - early colorectal cancer (defined as T1 or T2 according to TNMv6 criteria) and adenomatous polyps. Patients with familial adenomatous polyposis, inflammatory bowel disease or hereditary non-polyposis colon cancer were excluded. Specimens were analyzed ex-vivo using a modified electro-surgical hand piece with the aerosol aspirated into a Xevo G2-S QTof mass spectrometer (Waters Corporation). Multivariate analyses were used to create models which underwent cross-validation using SIMCA (V14, Umetrics, Sweden). Characteristic lipid species were identified using univariate statistics in R Studio (V1.0.44) and Metlin. An endoscopic set up was created using a standard endoscope for proof of concept. Summary of data 19 patients (12:7 F:M) were included with a median age of 74 (range 50-92). Six patients had T1/2 adenocarcinoma and 13 had adenomatous polyps. REIMS was able to accurately distinguish the presence of low grade dysplasia (LGD) vs high grade dysplasia (HGD) in adenomatous polyps (sensitivity 95.0%, specificity 100%). Phosphatidic acids (PA) 38:2 and 38:1 were more abundant in high vs low grade dysplasia (p=0.003). REIMS was also able to identify adenomatous polyps from early cancer (sensitivity 100%, specificity 96.3%). Phosphatidylethanolamine (PE) 36:1, phosphatidic acid (PA) 38:1, glucosylceramide (Glc-Cer) 30:1 and ceramide phosphoethanolamines (PE-Cer) d16:1(4E)/20:0 and d14:1(4E)/22:0 were associated with early cancer formation rather than adenomas (p<0.001, p<0.001, p=0.03, p=0.04 respectively). Endoscopic REIMS was successfully deployed in-vivo in six patients undergoing polypectomy. Spectra with good signal to noise ratio were acquired and the technology was able to correctly stratify adenomas. Conclusion Dysplastic adenomas exhibit mucosal lipid chemistry that is discrete from early colorectal cancer. PA, PE and Glc-Cer have potential use as diagnostic biomarkers. First in man studies of the endoscopic application of REIMS suggest it could serve as a real-time tool for early cancer detection based on in vivo analysis of the mucosal lipidome. Citation Format: Petra Paizs, Eftychios Manoli, Sam E. Mason, James L. Alexander, Zsolt Bodai, Emma White, Afeez Adebesin, Jonathan Hoare, Robert Goldin, Ara W. Darzi, James M. Kinross, Zoltan Takats. Rapid evaporative ionization mass spectrometry (REIMS) analysis of the mucosal lipidome has a high diagnostic accuracy for adenomas and early colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4536.