báo cáo hóa học: Mass spectrometry-based serum proteome pattern analysis in molecular diagnostics of early stage breast cancer

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báo cáo hóa học:" Mass spectrometry-based serum proteome pattern analysis in molecular diagnostics of early stage breast cancer"Journal of Translational Medicine BioMed Central Open AccessResearchMass spectrometry-based serum proteome pattern analysis inmolecular diagnostics of early stage breast cancerMonika Pietrowska†1, Lukasz Marczak†2, Joanna Polanska†3,Katarzyna Behrendt1, Elzbieta Nowicka1, Anna Walaszczyk1,Aleksandra Chmura1, Regina Deja1, Maciej Stobiecki2, Andrzej Polanski3,4,Rafal Tarnawski1 and Piotr Widlak*1Address: 1Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland, 2Polish Academy of Science, Institute ofBioorganic Chemistry, Poznan, Poland, 3Silesian University of Technology, Gliwice, Poland and 4Polish-Japanese Institute of InformationTechnology, Bytom, PolandEmail: Monika Pietrowska - m_pietrowska@io.gliwice.pl; Lukasz Marczak - lukasmar@ibch.poznan.pl;Joanna Polanska - joanna.polanska@polsl.pl; Katarzyna Behrendt - kbehrendt@io.gliwice.pl; Elzbieta Nowicka - enowicka@io.gliwice.pl;Anna Walaszczyk - awalaszczyk@io.gliwice.pl; Aleksandra Chmura - bialka@io.gliwice.pl; Regina Deja - markery@io.gliwice.pl;Maciej Stobiecki - mackis@ibch.poznan.pl; Andrzej Polanski - andrzej.polanski@polsl.pl; Rafal Tarnawski - rafaltarnawski@gmail.com;Piotr Widlak* - widlak@io.gliwice.pl* Corresponding author †Equal contributorsPublished: 13 July 2009 Received: 21 April 2009 Accepted: 13 July 2009Journal of Translational Medicine 2009, 7:60 doi:10.1186/1479-5876-7-60This article is available from: http://www.translational-medicine.com/content/7/1/60© 2009 Pietrowska et al; licensee BioMed Central Ltd.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Mass spectrometric analysis of the blood proteome is an emerging method of clinical proteomics. The approach exploiting multi-protein/peptide sets (fingerprints) detected by mass spectrometry that reflect overall features of a specimens proteome, termed proteome pattern analysis, have been already shown in several studies to have applicability in cancer diagnostics. We aimed to identify serum proteome patterns specific for early stage breast cancer patients using MALDI-ToF mass spectrometry. Methods: Blood samples were collected before the start of therapy in a group of 92 patients diagnosed at stages I and II of the disease, and in a group of age-matched healthy controls (104 women). Serum specimens were purified and the low-molecular-weight proteome fraction was examined using MALDI-ToF mass spectrometry after removal of albumin and other high- molecular-weight serum proteins. Protein ions registered in a mass range between 2,000 and 10,000 Da were analyzed using a new bioinformatic tool created in our group, which included modeling spectra as a sum of Gaussian bell-shaped curves. Results: We have identified features of serum proteome patterns that were significantly different between blood samples of healthy individuals and early stage breast cancer patients. The classifier built of three spectral components that differentiated controls and cancer patients had 83% sensitivity and 85% specificity. Spectral components (i.e., protein ions) that were the most frequent in such classifiers had approximate m/z values of 2303, 2866 and 3579 Da (a biomarker built from these three components showed 88% sensitivity and 78% specificity). Of note, we did not find a significant correlation between features of serum proteome patterns and established prognostic or predictive factors like tumor size, nodal involvement, histopathological grade, estrogen and progesterone receptor expression. In addition, we observed a significantly (p = 0.0003) increased Page 1 of 13 ...