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Cellular and Molecular Biology 5: Gene Expression 2

Abstract #125

Expression profiling of peripheral blood cells for early detection of breast cancer

The Norwegian Radium Hospital, Oslo, Norway, DiaGenic ASA, Oslo, Norway, Norwegian University of Life Sciences, Ås, Norway, Ullevål University Hospital, Oslo, Norway

Early detection of breast cancer is the key to successful treatment and patient survival. In a recently published study (Sharma et al. 2005), we demonstrate the potential use of gene expression profiling in peripheral blood cells (PBC) for early detection of breast cancer. Due to limited sample size and the use of in-house manufactured macroarrays in the initial study, the aim of the present study was to investigate whether the findings reported could be reproduced using a larger sample size and a commercially available microarray platform.Blood samples were collected in PAX tubes from 64 females diagnosed with breast cancer and 76 females with no reported sign of the disease. Total RNA was extracted and gene expression analyses were conducted using high density oligonucleotide arrays (Agilent Technologies) containing 22.000 probes. Expression data were analyzed using several statistical approaches: Partial Least Square Regression (PLSR) was used for model building while a novel approach combining double and triple cross validation (CV) was used to identify stable and relevant predictors and estimate their prediction efficiency. Based on the selected predictors, pathway analysis was conducted (PathwayAssist, Ariadne Genomics). We have identified a set of genes that discriminated breast cancer and non-breast cancer samples with an accuracy not significantly different than previously reported. In addition to some gene families reported earlier, the identified predictors also included novel gene families. Pathway analysis identified a number of pathways based on the selected genes. These pathways are currently being investigated more thoroughly to reveal possible tumor-blood interactions. This larger study supports the results from our previous study. These data suggest that breast cancer affects gene expression patterns in PBC already in early stages of disease development. A blood-based gene expression test can potentially be developed for early detection of breast cancer.