The identification and validation of biomarkers of disease or predisposition for disease facilitates, early detection, risk reduction, patient stratification and monitoring of treatment efficacy. Genomics has led the way in disease biomarker detection and monitoring, however there is still a need for fast, robust, inexpensive and easy to deploy blood tests. In recent years the discipline of lipidomics has expanded from a purely discovery focus to encompass a more hypothesis driven targeted approach. Combining these two approaches provides a mechanism to quickly translate discovery finding to clinical application. Key to the application of these methods is the development of a robust, reliable sample preparation and LC/MS methodology. Two facilitate this we have developed and applied two rapid platforms: 1) A 3-minute ion mobility enabled, accurate mass LC/MS discovery platform; 2) A quantitative LC/MS/MS lipid method capable of accurately measuring more than 500 lipids in less than 5 minutes. These two methodologies were applied to the analysis to breast, lung and bladder cancer samples. Despite the short analysis time the discovery methodology was capable of distinguishing between the cancer and healthy control groups in each case. The resulting lipid features of interest were then selected for quantification using the targeted approach. The incorporation of ion mobility into the discovery method increased feature detection by 50%, as a result of increased system resolution, it also improved the accuracy of database searching by providing superior fragment ion spectra. The IMS data was used to generate Collisional Cross Sectional Information for each Biomarkers this data was then compared to in-silico prediction of CCS values using in-house and publically available programs. The lung and bladder cancer analysis showed triglycerides (TG's) and glycolipids (GSL) as the primary markers of disease linking to Subsequent glycerophospholipid metabolism and glycerolipid metabolism. The phosphatidylcholines lipids, triglycerides and diglycerides showed lower expression in the breast cancer samples whereas the phosphatidylserine showed greater expression.

Identification of putitive bio markers of breast, liver, and bladder cancer with IOn mobility enabled LC/MS based metabolomics

2019 Fall National Meeting

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