Altered levels of sphingomyelins, ceramides, glycerophospholipids, and diacylglycerols in thymoma tissues

Abstract

Thymoma is a rare thymic epithelial tumor, and its pathogenesis and lipid characteristics are still unclear. In this study, non-targeted lipidomics study by ultra-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS) was conducted to analyze the alterations of lipids in 76 tissue samples from 24 thymoma, 14 thymic hyperplasia, and 1 thymic carcinoma (TC) patients. Sphingomyelins with 36–44 carbons (SM d36:1, SM d38:1, SM d40:1, SM d36:2, SM d38:2, SM d40:2, SM d41:2, SM d43:2, SM d44:2), medium, long and very-long chain ceramides (Cer d17:1/16:0, Cer d18:1/17:0, Cer d18:1/18:0, Cer d18:1/22:0, Cer d18:1/24:1, Cer d18:2/20:0, Cer d18:2/22:0), phosphatidylcholine (PC) 16:0_16:0, phosphatidylethanolamines (PE 16:0_16:0, PE 16:0_16:1, PE P-16:0_18:2), LPE 18:2, phosphatidylserine (PS) 18:1_22:0, diacylglycerols (DG 16:0_18:1 and DG 18:1_18:2) showed decreased levels, while polyunsaturated lysophosphatidylcholines (LPCs), PCs with long or very-long polyunsaturated acyl chains (PC 16:0_18:3, PC 18:0_22:5, PC 18:1_22:6, PC 15:0_18:2, PC 18:0_20:3, PC 18:0_20:4, PC 18:2_20:4, PC 20:2_20:4, PC 18:0_22:4, PC 20:4_22:4, PC O-18:0_20:4), part of identified PEs (PE P-16:0_18:1, PE P-18:0_20:4, PE P-16:0_22:6), DG 18:0_20:4, arachidyl carnitine, and 1-methylhistamine had increased levels in thymoma and 1 TC tissues compared to paired non-cancerous tissues. The most altered pathways in thymoma tissues were glycerophospholipid metabolism and sphingolipid metabolism. In addition, orthogonal partial least squares-discriminant analysis (oPLS-DA) based on 5 lipids (PC 18:0_20:3, PE 16:0_16:0, PC 18:0_22:5, PE P-16:0_18:1, and PC O-18:0_20:4) discriminated thymoma and 1 TC tissues from non-cancerous ones with 97.4 % accuracy, 100 % sensitivity, and 95.5 % specificity, showing a good discrimination ability.