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Comparative Plasma Proteomic Analysis of Patients with Multiple Myeloma Treated with Bortezomib-based Regimens


Authors: J. Čumová 1,2;  L. Jedličková 3;  D. Potěšil 3,4;  O. Šedo 4;  K. Stejskal 3;  A. Potáčová 1;  Z. Zdráhal 3;  R. Hájek 1,5,6
Authors‘ workplace: Babákova myelomová skupina, Ústav patologické fyziologie, LF MU Brno 1;  Oddělení klinických laboratoří, Nemocnice Blansko 2;  Oddělení funkční genomiky a proteomiky, Ústav experimentální biologie, PřF MU Brno 3;  Výzkumná skupina Proteomika CF, Mendelovo centrum genomiky a proteomiky rostlin, Středoevropský technologický institut, MU Brno 4;  Laboratoř experimentální hematologie a buněčné imunoterapie, Oddělení klinické hematologie, FN Brno 5;  Interní hematoonkologická klinika, LF MU a FN Brno 6
Published in: Klin Onkol 2012; 25(1): 17-25
Category: Original Articles

Overview

Backgrounds:
Recently, the term biomarker has become, especially in connection with the term clinical proteomics, one of the most frequent terms in the field of biomedical research. The aim of this work was to select an appropriate pre-fractionation method of blood plasma prior to a subsequent proteomic analysis of low-abundant fraction of proteins by two dimensional gel electrophoresis (2-DE) and mass spectrometry to improve the resolution of 2-DE maps and protein identification.

Materials and Methods:
First, we compared two prefractionation methods (MARS versus ProteoMiner) preceding 2-DE analysis using 10 blood plasma samples. Based on the results of the comparative experiments, low-abundant plasma protein fractions from 18 multiple myeloma patients treated with bortezomib were analyzed. Patients were divided into two groups: a group resistant to chemotherapy (9 patients – disease progression, stable disease) and a group with positive clinical response (9 patients – complete and partial remission).

Results and Conclusion:
Samples prefractioned by ProteoMiner method yielded 2-DE maps with a significantly increased number of detected protein spots, as compared to immunodepletion method MARS (Multiple Affinity Removal System). Between groups of chemoresistant and sensitive patients treated with bortezomib, 15 differently intense spots were revealed by image analysis. These spots were found to correspond to 10 proteins, as confirmed by mass spectrometry. Seven proteins had significantly lower protein level in the group of chemosensitive patients (serum amyloid P, fibrinogen – gamma chain, retinol-binding protein 4, complement factor C4-A, apolipoprotein E, carboxypeptidase N and complement factor H-related protein 1) and 3 proteins showed significantly higher levels of protein (or were only detected) in the group of chemosensitive patients (serum paraoxonase 1, alpha-1-antitrypsin and complement factor B).

Key words:
multiple myeloma – proteomics – two dimensional gel electrophoresis – plasma – protein – bortezomib

This work was supported by grants of Ministry of Education, Youth and Sports of the CR (LC06027 a MSM0021622434) and IGA MZ (NS9683) and NT12130) and grant of The Czech Science Foundation GAP304/10/1395..

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
3. 6. 2011

Accepted:
8. 9. 2011


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