Concurrent lipidomics and proteomics on malignant plasma cells from multiple myeloma patients: Probing the lipid metabolome

Autor: Joel Collins, Ahmed Mohamed, Paula Marlton, Federico Torta, Robert Bird, Markus R. Wenk, Peter Mollee, Thomas Stoll, Hui Jiang, Michelle M. Hill, Kate A. Markey, Jeffrey Molendijk
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Proteomics
Proteome
Pilot Projects
Biochemistry
Mass Spectrometry
Plasma Cell Disorders
Hematologic Cancers and Related Disorders
Transcriptome
White Blood Cells
Database and Informatics Methods
chemistry.chemical_compound
0302 clinical medicine
Recurrence
Animal Cells
Medicine and Health Sciences
Macromolecular Structure Analysis
Chromatography
High Pressure Liquid
Multiple myeloma
0303 health sciences
Multidisciplinary
Lipid Analysis
Proteomic Databases
Hematology
Genomics
Lipids
3. Good health
Myelomas
medicine.anatomical_structure
Oncology
Area Under Curve
030220 oncology & carcinogenesis
Phosphatidylcholines
Medicine
Cellular Types
Multiple Myeloma
Transcriptome Analysis
Research Article
Ceramide
Science
Immune Cells
Plasma Cells
Immunology
Research and Analysis Methods
03 medical and health sciences
Lipidomics
Genetics
medicine
Metabolome
Humans
Myelomas and Lymphoproliferative Diseases
Molecular Biology
030304 developmental biology
Blood Cells
business.industry
Cancers and Neoplasms
Biology and Life Sciences
Computational Biology
Lipid metabolism
Cell Biology
Lipid Metabolism
Genome Analysis
medicine.disease
030104 developmental biology
Biological Databases
Metabolism
ROC Curve
chemistry
Cancer research
Bone marrow
business
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 1, p e0227455 (2020)
DOI: 10.1101/702993
Popis: BackgroundMultiple myeloma (MM) is a hematological malignancy characterized by the clonal expansion of malignant plasma cells. Though durable remissions are possible, MM is considered incurable, with relapse occurring in almost all patients. There has been limited data reported on the lipid metabolism changes in plasma cells during MM progression. Here, we evaluated the feasibility of concurrent lipidomics and proteomics analyses from patient plasma cells, and report these data on a limited number of patient samples, demonstrating the feasibility of the method, and establishing hypotheses to be evaluated in the future.MethodsPlasma cells were purified from fresh bone marrow aspirates using CD138 microbeads. Proteins and lipids were extracted using a bi-phasic solvent system with methanol, methyl tert-butyl ether, and water. Untargeted proteomics, untargeted and targeted lipidomics were performed on 7 patient samples using liquid chromatography-mass spectrometry. Two comparisons were conducted: high versus low risk; relapse versus newly diagnosed. Proteins and pathways enriched in the relapsed group was compared to a public transcriptomic dataset from Multiple Myeloma Research Consortium reference collection (n=222) at gene and pathways level.ResultsFrom one million purified plasma cells, we were able to extract material and complete untargeted (∼6000 and ∼3600 features in positive and negative mode respectively) and targeted lipidomics (313 lipids), as well as untargeted proteomics analysis (∼4100 reviewed proteins). Comparative analyses revealed limited differences between high and low risk groups (according to the standard clinical criteria), hence we focused on drawing comparisons between the relapsed and newly diagnosed patients. Untargeted and targeted lipidomics indicated significant down-regulation of phosphatidylcholines (PCs) in relapsed MM. Although there was limited overlap of the differential proteins/transcripts, 76 significantly enriched pathways in relapsed MM were common between proteomics and transcriptomics data. Further evaluation of transcriptomics data for lipid metabolism network revealed enriched correlation of PC, ceramide, cardiolipin, arachidonic acid and cholesterol metabolism pathways to be exclusively correlated among relapsed but not in newly-diagnosed patients.ConclusionsThis study establishes the feasibility and workflow to conduct integrated lipidomics and proteomics analyses on patient-derived plasma cells. Potential lipid metabolism changes associated with MM relapse warrant further investigation.
Databáze: OpenAIRE
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