Desorption electrospray ionisation mass spectrometry imaging for the lipidomic study of oesophageal adenocarcinoma and lymph node metastases

Abstract

Emerging evidence has demonstrated lipid composition differences in cancer cells versus that of benign tissue. The observed changes have been attributed to de novo lipogenesis, a metabolic process which occurs in cancer due to increased demands of cell proliferation. The specific lipid differences are not fully understood but their investigation has been made feasible through the development of novel analytical technologies. In this research, the application of Desorption Electrospray Ionisation-Mass Spectrometry (DESI-MS) for the analysis of lipids in human tissue has been investigated. The aim of this thesis was to evaluate the instrument for cancer tissue analysis and undertake a lipidomic study of oesophageal adenocarcinoma (OA) and its associated lymph node metastases.

Optimal geometric/electrospray solvent parameters have been investigated and optimised to maximize the number of detected lipid species and associated total ion current for DESI-MS of human tissue. Assessments of repeatability and reproducibility measurements of lipid ion intensities have also been undertaken. The analytical performance of the instrument was compared with the gold standard Ultra Performance Liquid Chromatography-Electrospray Ionisation-Mass Spectrometry. In the first clinical study, DESI-MS lipidomic profiling was combined with immunohistochemical assay and cell functional studies to investigate the associations of cancer-related lipogenesis with the expression of glycerophospholipids in OA. In the second clinical study, DESI-MS has been used for the objective identification of metastases within lymph nodes based on the average lipidomic profile of OA from the primary tumour site.

In conclusion, DESI-MS has been validated for the purpose of lipidomic analysis and demonstrated a distinct molecular profile of OA, which has also been utilised in the objective detection of lymph node metastases.