Differential Expression Of Microfilamental Network-Associated Proteins In Circulating Leukocytes Of Patients With Benign And Malignant Breast Tumors Versus Controls As Revealed By Clinical Proteomics: Potential Application To Early And Predictive Diagnosis

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #2037 Background: Breast cancer is one of the most frequent tumors world-wide. Early diagnosis has been demonstrated to be highly beneficial for significantly enhanced therapeutic efficiency and possibly full recovery. Currently applied diagnostic approaches are frequently not able to recognize very early stages in tumor development that impair the outcome. Our efforts are focused on the creation of early and even predictive diagnosis of breast cancer based on an application of advanced minimal-invasive molecular biotechnological approaches such as pathology-specific blood proteome. Material and methods: Protein expression profiling was performed in circulating leukocytes isolated from fresh blood samples of age-matched female patients with invasive breast cancer (9 invasive lobular and 10 invasive ductal tumors), benign breast tumors (11 patients) and 9 healthy controls. In patients with all kinds of breast tumors, blood samples were taken before core needle biopsy of the lump. Comparative protein mapping in circulating leukocytes was performed by 2D-PAGE followed by MALDI-TOF-analysis of differentially expressed protein spots. Corresponding expression levels of identified proteins were further measured using Western-blot quantification. Results: Molecular patterns were identified in circulating leukocytes and found to be specific for breast tumor patients. The results achieved at all levels were highly reproducible. The pathology specific patterns comprise microfilamental network-associated proteins: Calgranulins, LyGDI, RhoA, profilin, and actins. Calgranulin, RhoA, and profilin expression levels were significantly higher in healthy controls compared to patients with breast tumors, regardless the tumor malignancy (p=0.002 p<0.001 and p=0.025, respectively). Moreover, calgranulin expression levels discriminated well among lobular carcinomas, benign tumors, ductal carcinomas, and controls. Strong correlation between profilin and RhoA expression levels was demonstrated in all individual samples. Noteworthy, significant difference for expression levels of actins between patients with both malignant and benign tumors versus controls was demonstrated. Conclusions: Microfilamental network-associated proteins identified here are involved in the regulation of a variety of cellular processes; they are functionally linked with each other and known to be highly relevant for all stages of tumorigenesis beginning with precancerous lesions and including activated metastasing potential. Statistical analysis demonstrated high specificity of the tumor-related molecular patterns. These findings are currently considered for a development of novel highly sensitive minimal-invasive approaches for early diagnosis of breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2037.