Serum lipidomics for exploring biomarkers of bortezomib therapy in patients with multiple myeloma

• Published in: Cancer science 2019-10, Vol.110 (10), p.3267-3274
• Main Authors: Maekawa, Keiko, Ri, Masaki, Nakajima, Miki, Sekine, Akihiro, Ueda, Ryuzo, Tohkin, Masahiro, Miyata, Naoki, Saito, Yoshiro, Iida, Shinsuke
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers; Biomarkers, Tumor - blood; Bortezomib; Bortezomib - administration & dosage; Bortezomib - adverse effects; Cholesterol; Cholesterol Esters - blood; Chromatography; Dexamethasone; Esters; Fatty acids; Female; Fourier transforms; Glycerophospholipids - blood; Humans; Inflammation; Kidney cancer; Lipid metabolism; lipidomics; Lipids; Lipids - blood; Male; Mass spectrometry; Metabolism; Metabolites; Metabolomics - methods; Middle Aged; Multiple myeloma; Multiple Myeloma - blood; Multiple Myeloma - chemistry; Multiple Myeloma - drug therapy; Myelin; Original; Oxidation; Pain; Patients; Peripheral Nervous System Diseases - chemically induced; Peripheral neuropathy; Pharmaceuticals; Phospholipids; Polyunsaturated fatty acids; Proteasome inhibitors; R&D; Research & development; Research funding; response rate; Scientific imaging; Serum levels; Severity of Illness Index; Software; Sphingolipids; Sphingolipids - blood; Treatment Outcome
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.14178

Although the proteasome inhibitor bortezomib (BTZ) shows excellent efficacy in multiple myeloma (MM), a fraction of patients has a suboptimal or no response to this agent. In addition, BTZ‐induced peripheral neuropathy (BiPN), a frequent side‐effect of this therapy, limits its use in some patients. This study aimed to explore serum lipid biomarker candidates to predict the response to BTZ and the severity of BiPN. Fifty‐nine serum samples were collected from patients with MM prior to receiving BTZ plus low‐dose dexamethasone therapy. Serum levels of phospholipids, sphingolipids, neutral lipids, and polyunsaturated fatty acids and their oxidation products were measured by a comprehensive lipidomic study. Overall, 385 lipid metabolites were identified in patients’ sera; lower levels of several glycerophospholipids, sphingolipids, and cholesteryl esters were associated with a poor treatment response. Metabolites related to platelet‐activating factor biosynthesis and cholesterol metabolism appeared particularly relevant. Furthermore, several lysophosphatidylcholines, phosphatidylcholines, ceramides, neutral lipids, and oxidative fatty acids were significantly increased or decreased in patients with BiPN grades ranging from G0 to G3. Among these compounds, mediators reportedly inducing myelin breakdown and stimulating inflammatory responses were prominent. Although further study is necessary to validate these biomarker candidates, our results contribute to the development of predictive biomarkers for response to BTZ treatment, or ensuing severe BiPN, in patients with MM. This study aimed to explore lipid biomarker candidates to predict the response to bortezomib (BTZ) and the severity of BTZ‐induced peripheral neuropathy (BiPN) in multiple myeloma (MM) patients. A comprehensive lipidomic analysis was carried out using pretreatment sera from MM patients who received BTZ plus low‐dose dexamethasone therapy. The response‐associated metabolites appear to be involved in platelet‐activating factor biosynthesis and cholesterol metabolism, whereas the BiPN‐associated metabolites seem to be implicated in the myelin breakdown and inflammatory responses.