Serum lipidomics for exploring biomarkers of bortezomib therapy in patients with multiple myeloma.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ blood
Bortezomib
/ administration & dosage
Cholesterol Esters
/ blood
Female
Glycerophospholipids
/ blood
Humans
Lipids
/ blood
Male
Metabolomics
/ methods
Middle Aged
Multiple Myeloma
/ blood
Peripheral Nervous System Diseases
/ chemically induced
Severity of Illness Index
Sphingolipids
/ blood
Treatment Outcome
bortezomib
lipidomics
multiple myeloma
peripheral neuropathy
response rate
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
24
04
2019
revised:
06
08
2019
accepted:
15
08
2019
pubmed:
25
8
2019
medline:
12
10
2019
entrez:
25
8
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31444836
doi: 10.1111/cas.14178
pmc: PMC6778623
doi:
Substances chimiques
Biomarkers, Tumor
0
Cholesterol Esters
0
Glycerophospholipids
0
Lipids
0
Sphingolipids
0
Bortezomib
69G8BD63PP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3267-3274Subventions
Organisme : Ministry of Education, Culture, Sports, Science, and Technology
ID : 16K07179
Organisme : Ministry of Education, Culture, Sports, Science, and Technology
ID : 16K09855
Organisme : National Cancer Center Research and Development Fund
ID : 26-A-4
Organisme : Accelerating Regulatory Science Initiative from the Ministry of Health, Labour and Welfare
Organisme : Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development, AMED
ID : 15ck0106077h0002
Organisme : Hoansha Foundation
Informations de copyright
© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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