多発性骨髄腫における非標的メタボロミクスに基づく代謝特性

Non-targeted metabolomics based on ultra-performance liquid chromatography mass spectrometry (UPLC-MS) platform was used to study the metabolic characteristics of multiple myeloma (MM) patients, and explore potential new metabolic mechanisms affecting the occurrence and development of MM.

The study enrolled 42 MM patients, including 21 newly diagnosed (ND) patients and 21 relapsed patients (RP), and 21 age-sex matched healthy controls (HC) as subjects. UPLC-MS analysis platform was used to detect small molecule metabolites in serum of the subjects. Principal component analysis (PCA), orthogonal partial least-squared discriminant analysis (OPLS-DA) and 200 random permutations were used to analyze the differences of metabolic profiles among groups. Identification of differential metabolites was completed in the Human Metabolome Database (HMDB) and abnormal metabolic pathway analysis was performed using the KEGG database.

The metabolic profiles of MM patients and healthy controls were significantly separated in both PCA and OPLS-DA models, while the metabolic profiles of newly diagnosed and relapsed MM patients were significantly separated only in OPLS-DA model. In ND vs HC, RP vs HC and RP vs ND cohorts, 19, 24 and 18 differential metabolites were identified respectively, mainly sphingolipids, glycerophospholipids and fatty acyl amino acids. The metabolic pathway abnormalities in newly diagnosed and relapsed MM patients were mainly manifested in sphingolipid metabolism and glycerophospholipid metabolism compared to healthy controls. Compared with newly diagnosed MM patients, relapsed MM patients were mainly manifested in sphingolipid metabolism and ether-lipid metabolism.

The metabolic profiles of MM patients are significantly different from those of healthy people. Relapsed MM patients and newly diagnosed MM patients have similar metabolic profiles, but there are still some differences. Glycerophospholipid metabolism, sphingolipid meta- bolism and ether-lipid metabolism may play important biological roles in the occurrence and development of MM.