Down-regulation of microfilamental network-associated proteins in leukocytes of breast cancer patients: potential application to predictive diagnosis.
BACKGROUND
Breast cancer is one of the most frequent tumors worldwide. Currently applied diagnostic approaches are frequently not able to recognize early stages in tumor development therefore impairing outcomes. The focus of this study is the creation of a non-invasive predictive diagnostic approach by pathology-specific blood proteome analysis.


METHODS
Circulating leukocytes were isolated from fresh blood samples of breast cancer patients, benign breast pathologies and healthy controls. In patients with all kinds of breast pathologies, blood samples were taken before core needle biopsy of the lump. Comparative protein mapping was performed by 2D-PAGE followed by MALDI-TOF analysis and Western-blot quantification of differentially expressed protein spots.


RESULTS
By protein mapping, 64 protein spots were identified. Pathology-specific differential expression patterns comprised microfilamental network-associated proteins: Calgranulin A (S100), LyGDI (Rho GDIbeta), RhoA and profilin 1. RhoA and profilin values discriminated between healthy controls and patients with all breast pathologies.


CONCLUSIONS
Microfilamental network-associated proteins are involved in the regulation of a variety of central cellular processes functionally linked with each other and known to be highly relevant for all stages of tumorigenesis including precancerous lesions and metastases. Pathology-related molecular patterns are currently considered for the creation of a novel highly sensitive minimally-invasive approach for predictive diagnosis of breast cancer.
Braun
Michael
M
Department of Radiology, Division of Molecular/Experimental Radiology, University of Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany.
Fountoulakis
Michael
M
Papadopoulou
Ageliki
A
Vougas
Kostas
K
Seidel
Ilka
I
Höller
Tobias
T
Yeghiazaryan
Kristina
K
Schild
Hans H
HH
Kuhn
Walther
W
Golubnitschaja
Olga
O
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D016022:Case-Control Studies; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism; D011379:Prognosis; D020543:Proteome; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; D020543:Proteome