Untargeted Lipidomics Reveals Specific Lipid Abnormalities 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 problems such as headaches, visual
field defects, 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 to date. 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 eight null cell adenomas (NCAs)
and eight oncocytomas (OCMs) and of five normal pituitary glands as
the control (Ctrl) using nontargeted lipidomics based on ultrahigh-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, which 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 vs Ctrl.
Our results indicate that AA-PLs may have diagnostic potential for
OCM.