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Expression profiling of peripheral blood cells for early detection

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Existing methods to detect breast cancer in asymptomatic patients have limitations, and there is a need to develop more accurate and convenient methods. Especially, an accurate method for breast cancer detection based on peripheral blood as a clinical sample will be highly desirable because of the easy accessibility and less-invasive nature by which samples can be obtained.

Results demonstrating that peripheral blood can be used to develop a gene expression based test for early detection of breast cancer will be presented. The rationale for using blood cells as monitors for a malignant disease elsewhere in the body is based on the hypothesis that a malignant growth will cause characteristic changes in the biochemical environment of blood. These changes will affect the expression pattern of certain genes in blood cells.

We initially conducted a pilot study where the expression pattern of 1368 genes in peripheral blood cells of 24 females with breast cancer and 32 females with no signs of this disease were analyzed using macroarrays and the expression data analyzed by PAM. The results were validated using a standard leave-one-out cross-validation approach. We were able to identify a set of genes that correctly predicted the diagnostic class in at least 82% of the samples. The majority of the identified genes had a decreased expression in samples from breast cancer patients, and predominantly encoded proteins implicated in ribosome production and translation control. In contrast, the expression of some defence-related genes was increased in samples from breast cancer patients.

In order to revalidate these findings and to increase the repertoire of informative genes, we have now extended the study with a larger number of breast cancer and non-breast cancer samples and used Agilent WG oligo arrays for large-scale gene expression analysis. The preliminary analysis of the data supports our previous finding that a blood-based gene expression test can potentially be developed to detect breast cancer in asymptomatic patients.

References

  1. 1.

    Sharma P, Sahni NS, Tibshirani R, Skaane P, Urdal P, Berghagen H, Jensen M, Kristiansen L, Moen C, Sharma P, et al: Early detection of breast cancer based on gene expression patterns in peripheral blood cells. Breast Cancer Res. 2005, 7: R634-R644. 10.1186/bcr1203.

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Børresen-Dale, A., Sharma, P. Expression profiling of peripheral blood cells for early detection. Breast Cancer Res 7, S.20 (2005) doi:10.1186/bcr1063

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Keywords

  • Breast Cancer
  • Breast Cancer Patient
  • Asymptomatic Patient
  • Peripheral Blood Cell
  • Oligo Array