Untargeted lipidomics reveals specific lipid abnormality in nonfunctioning human pituitary adenomas.

The pituitary gland is a small but important organ located in the base of the brain. Although mostly noncancerous, pituitary adenomas (PAs) can cause serious health upsets such as headaches, visual field defect, double vision, and hypopituitarism by invasion of regional structures. Nonfunctioning PAs (NFPAs) approximately account for one third of PAs manifested by no circulating hormone hypersecretion. Lipid reprogramming has been recognized as a hallmark of tumor cells and proven to play a crucial role in tumorigenesis. However, the lipid molecular pathogenesis of NFPAs has remained obscure yet. To uncover lipid alterations that may contribute to the development of NFPAs and define their molecular characteristics, we investigated tissue lipids of patients with NFPAs including 8 null cell adenomas (NCAs) and 8 oncocytomas (OCMs) and of 5 normal pituitary glands as the control (Ctrl) using non-targeted lipidomics based on ultra-high performance liquid chromatography-Orbitrap Q Exactive HF mass spectrometry. The lipidomic results were further validated in another set of subjects consisting of 8 NCAs, 10 OCMs and 6 Ctrls to define crucial lipids discriminating NFPAs from the normal pituitary tumors. Lipidomic analyses revealed that OCM showed more pronounced changes in lipid compositions than NCA and Ctrl. As expected, mitochondria abundant cardiolipins were remarkably increased in OCM that was accordant with the biochemical evidence of mitochondria hyperplasia in OCM. Significantly increased levels of phospholipids (PLs), especially arachidonic acid (AA)-enriched PLs were unique characteristics of lipid profiling in OCM versus Ctrl. Our results indicate that AA-PLs may have diagnostic potential for OCM.