Lipidomic Plasticity in Testicular Cancer Reflects Diagnostic Signatures in Tissue and Plasma: A Pilot Study

BACKGROUND: Diagnosis and prognosis of testicular cancer remain challenging due to lack of reliable diagnostic markers. While lipidomic alterations have been explored in other cancers, their application to testicular cancer is limited. Lipidomics may offer valuable insights, as lipid changes in blood can reflect tumor development. OBJECTIVES: The goal was to assess the lipid profile changes in testicular tissue (with and without tumor) and plasma, from testicular cancer patients compared with healthy controls, to identify key differences. MATERIALS AND METHODS: In this study, untargeted C18 RP-LC-MS lipidomics approach was used to assess the plasticity of lipid profile in testicular tissue (with and without tumor) and plasma, from testicular cancer patients. RESULTS: Principal component analysis revealed a clear discrimination of the samples. Malignant tissue showed significant upregulation of several phosphatidylcholine (PC) and lyso-phosphatidylcholine (LPC) species mainly esterified to saturated and monounsaturated fatty acids (FAs), while phosphatidylinositol, phosphatidylserine, and phosphatidylglycerol species containing polyunsaturated FA were downregulated when compared with nontumor tissues from the same patients. Plasma samples from patients with testicular cancer showed increased levels of PC, LPC, and some sphingomyelin (SM) species, and decreased triacylglycerol (TG) and diacylglycerol (DG) species when compared with healthy controls. Five lipid species, TG 52:6, TG 56:7, phosphatidylethanolamine (PE) P-40:3/PE O-40:4, PC 42:3, and PC P-37:2, showed consistent differential expression across both tissue and plasma. CONCLUSION: These findings highlight the modification of lipid metabolism in testicular cancer, offering novel insights into the disease's pathophysiology and supporting the potential of lipids as diagnostic markers for its detection and monitoring.