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Proteomics-based strategies to identify proteins relevant to chronic lymphocytic leukemia
journal contribution
posted on 2023-06-10, 04:55 authored by Suliman A Alsagaby, Sanjay Khanna, Keith W Hart, Guy Pratt, Christopher Fegan, Christopher PepperChristopher Pepper, Ian A Brewis, Paul BrennanChronic lymphocytic leukemia (CLL), a malignant B-cell disorder, is characterized by a heterogeneous clinical course. Two-dimensional nano liquid chromatography (2D-nano-LC) coupled with matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-TOF/TOF MS) (LC-MALDI) was used to perform qualitative and quantitative analysis on cellular extracts from 12 primary CLL samples. We identified 728 proteins and quantified 655 proteins using isobaric tag-labeled extracts. Four strategies were used to identify disease-related proteins. First, we integrated our CLL proteome with published gene expression data of normal B-cells and CLL cells to highlight proteins with preferential expression in the transcriptome of CLL. Second, as CLLs outcome is heterogeneous, our quantitative proteomic data were used to indicate heterogeneously expressed proteins. Third, we used the quantitative data to identify proteins with differential abundance in poor prognosis CLL samples. Fourth, hierarchical cluster analysis was applied to identify hidden patterns of protein expression. These strategies identified 63 proteins, and 4 were investigated in a CLL cohort (39 patients). Thyroid hormone receptor-associated protein 3, T-cell leukemia/lymphoma protein 1A, and S100A8 were associated with high-risk CLL. Myosin-9 exhibited reduced expression in CLL samples from high-risk patients. This study shows the usefulness of proteomic approaches, combined with transcriptomics, to identify disease-related proteins.
History
Publication status
- Published
Journal
Journal of Proteome ResearchISSN
1535-3893Publisher
American Chemical Society (ACS)External DOI
Issue
11Volume
13Page range
5051-5062Event location
United StatesDepartment affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2022-09-30Usage metrics
Categories
No categories selectedKeywords
CLLS100A8TCL-1TR150iTRAQ-based quantitative proteomicsmyosin-9Aged80 and overBiomarkersTumorCalgranulin ACluster AnalysisFollow-Up StudiesHumansKaplan-Meier EstimateLeukemiaLymphocyticChronicB-CellT-CellMicroarray AnalysisMiddle AgedMolecular Motor ProteinsMyosin Heavy ChainsPrognosisProteinsProteomicsReproducibility of ResultsSpectrometryMassMatrix-Assisted Laser Desorption-IonizationTandem Mass Spectrometry