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RESEARCH PRODUCT

Genomic and Proteomic Integrated Approach to Study Breast Cancer: Differences in Patients negative and Positive to 18F-FDG PET Screening

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Breast cancer rather presents distinct subtypes associated with different clinical outcomes. Understanding this heterogeneity is a key factor for the development of targeted preventative and therapeutic interventions (Rakha et al 2008). 18Ffluoro- 2-deoxy-D-glucose Positron Emission Tomography (18F-FDG PET) has been evaluated in breast cancer to characterize primary tumors, lymph node staging and patients follow-up after surgery, chemotherapy and/or external radiotherapy (Lind et al 2004). PET is a molecular imaging technique sensitive to functional or metabolic changes in tissues. Since functional changes precede anatomical changes, FDG PET has the capability to detect viable tumor tissue early through its elevated glucose metabolism in comparison with the surrounding normal tissues (Plathow et al 2008). A major advantage of FDG PET imaging compared to conventional imaging is that it screens the entire patient for local recurrence, lymph node metastases and distant metastases during a single whole-body examination using a single injection of tracer, with a reported average sensitivity and specificity of 96% and 77%, respectively (Scheidhauer et al 2004). A general limitation of this new application of this technology are false negative results ( not all breast cancer patients are positive to 18F FDG PET analysis) and interpretative pitfalls due to physiological tracer distributions. Proteomic and transcriptomic platforms both play important roles in cancer research, with differing strengths and limitations. Here, we describe a proteo-transcriptomic integrative strategy to profile patients positive and negative to PET analysis by combining differentially expressed proteins with gene expression profile. In this study, 2D-Difference in Gel Electrophoresis (2D-DIGE), mass spectrometry and DNA-microarray analysis by Agilent platform, performed on the same sample, were utilized to compare patients positive and negative to 18F-FDG PET analysis. Our study illustrates how the systematic integration of proteomic and transcriptomic data could open new avenues to improve diagnosis and follow up and to accelerate cancer biomarkers discovery.