TMET-04. METABOLOMICS ANALYSIS IN FUNCTIONING AND SILENT CORTICOTROPH ADENOMAS USING A TWO-DIMENSIONAL NANOMATERIAL HIGH-THROUGHPUT PLATFORM

Abstract Functioning pituitary corticotroph adenomas (CAs) originated from T-PIT lineage with an ACTH-positive staining cause Cushing’s Disease. However, silent CAs (SCAs) baring the same histological features present clinically non-functioning with more aggressive courses. Metabolites within the tumor microenvironment play critical roles in regulating tumor behaviors and responses to therapy. Understanding their distribution and concentration provides valuable insights for diagnosis and treatment. This study investigated metabolite patterns in functioning and silent CAs. We developed a novel two-dimensional nanomaterial platform for enhanced surface-assisted laser desorption/ionization mass spectrometry. Utilizing this platform, we analyzed the metabolomes of three functioning CAs and three SCAs. Our platform exhibited exceptional sensitivity and stability in detecting metabolite molecules. Analysis of the metabolomes revealed distinct spatial distributions and peak intensity of various metabolites, including carbohydrates, amino acids, organic acids, nucleotides, and their precursors. Notably, certain metabolites such as tryptophol, clopidogrel carboxylic acid, DG(20:4(8Z,11Z,14Z,17Z)-2OH(5S,6R)/0:0/i-16:0), S-(-)-ureidoglycolate, and PC(20:4(5Z,7E,11Z,14Z)-OH(9)/14:1(9Z)) were significantly enriched in functioning CAs compared to SCAs, while others, including Cer(d18:1/16:0), Dihydrocytochalasin B, and LysoPC(O-18:0/0:0), exhibited higher peak intensity in SCAs. Overall, our findings underscored the existence of unique metabolomic signatures distinguishing functioning CAs and SCAs. Heterogeneous metabolite distributions among functioning CAs and SCAs were revealed by our novel nanomaterial high-throughput platform, and unique metabolic signatures were identified. Metabolomics analysis holds promise for precise biomedical diagnostics and individualized therapeutic strategies in functioning and silent CAs.