Serum lipidomics for exploring biomarkers of bortezomib therapy in patients with multiple myeloma
| Autor: | Masahiro Tohkin, Naoki Miyata, Keiko Maekawa, Ryuzo Ueda, Shinsuke Iida, Akihiro Sekine, Masaki Ri, Yoshiro Saito, Miki Nakajima |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research response rate peripheral neuropathy Glycerophospholipids Pharmacology Severity of Illness Index Bortezomib 03 medical and health sciences 0302 clinical medicine Clinical Research Lipidomics medicine Biomarkers Tumor Humans Metabolomics Dexamethasone Multiple myeloma Aged chemistry.chemical_classification Aged 80 and over Sphingolipids business.industry Peripheral Nervous System Diseases General Medicine Original Articles Middle Aged medicine.disease Sphingolipid Lipids multiple myeloma 030104 developmental biology Treatment Outcome Oncology chemistry 030220 oncology & carcinogenesis Proteasome inhibitor Biomarker (medicine) lipidomics Original Article Female Cholesterol Esters business medicine.drug Polyunsaturated fatty acid |
| Zdroj: | Cancer Science |
| ISSN: | 1349-7006 1347-9032 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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