Lipidomic profiling of endometrial cancer using desorption electrospray ionization mass spectrometry imaging

Novel technologies are required to improve endometrial cancer diagnosis and enhance the early detection of preinvasive precursors. Herein, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was used to differentiate malignant from benign endometrial tissues and assess lipidomic differences among patients with obesity and diabetes. Reverse phase protein array (RPPA) analysis was performed in the same patients to gain insights into the altered signaling pathways and investigate the protein expression levels in endometrial cancer cases and controls. Tissues from 64 women (50 cancer, 14 benign) were analyzed with DESI-MSI achieving 90% sensitivity and 93% specificity. Discriminatory spectral features were primarily phospholipids [phosphatidic acid (PA), phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylinositol (PI)], all elevated in cancer. Proteomics revealed upregulated proteins linked to commonly dysregulated pathways in endometrial cancer, namely PI3K/AKT/mTOR, MAPK/RAS, and Wnt signaling pathways. Lipidomic differences were found between high- (obesity/diabetes) and low-risk phenotypes (no obesity/diabetes), with PE and PS elevated in high-risk benign and PE reduced in high-risk cancer cases. A single phospholipid (PE(O-38:4)) was found as discriminatory in both normal and cancer cohorts, which may serve as biomarker in women with benign histology at high-risk of developing endometrial cancer. This study reports the application of DESI-MSI for lipidomic characterisation of endometrial cancer.