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

Abstract

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.

• Authors: Keiko Maekawa, Masaki Ri, Miki Nakajima, Akihiro Sekine, Ryuzo Ueda, Masahiro Tohkin, Naoki Miyata, Yoshiro Saito, Shinsuke Iida
• Journal: Cancer science (Cancer Sci) Vol. 110 Issue 10 Pg. 3267-3274 (Oct 2019) ISSN: 1349-7006 [Electronic] England
• PMID: 31444836 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Biomarkers, Tumor
• Cholesterol Esters
• Glycerophospholipids
• Lipids
• Sphingolipids
• Bortezomib

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (blood)
• Bortezomib (administration & dosage, adverse effects)
• Cholesterol Esters (blood)
• Female
• Glycerophospholipids (blood)
• Humans
• Lipids (blood)
• Male
• Metabolomics (methods)
• Middle Aged
• Multiple Myeloma (blood, chemistry, drug therapy)
• Peripheral Nervous System Diseases (chemically induced)
• Severity of Illness Index
• Sphingolipids (blood)
• Treatment Outcome