Open AccessSerum lipidomics for exploring biomarkers of bortezomib therapy in patients with multiple myeloma
Author(s) -
Maekawa Keiko,
Ri Masaki,
Nakajima Miki,
Sekine Akihiro,
Ueda Ryuzo,
Tohkin Masahiro,
Miyata Naoki,
Saito Yoshiro,
Iida Shinsuke
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.14178
Subject(s) - lipidomics , bortezomib , sphingolipid , biomarker , multiple myeloma , pharmacology , medicine , lipid metabolism , dexamethasone , endocrinology , chemistry , biochemistry
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 (Bi PN ), 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 Bi PN . 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 Bi PN 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 Bi PN , in patients with MM .