Breast cancer is a major health issue, affecting annually approximately 1.4 million women worldwide. It is a highly heterogeneous disease with the different subtypes having distinct clinical outcomes and different sensitivity to various treatment modalities. The focus of the present dissertation was the identification of novel proteomic prognostic markers for patients with early stage breast cancer.
Three different approaches to identify potential prognostic markers were undertaken. First, we hypothesized that since different breast cancer subtypes have distinct clinical outcomes, breast cancer subtype-specific proteins may retain prognostic potential. Second, given the central role of estrogen signaling in breast epithelial cell biology, we hypothesized that estrogen-regulated proteins may be useful in predicting patient outcome. Finally, we hypothesized that genes related to survival based on meta-analyses of publicly available breast cancer tissue microarray data, may also demonstrate prognostic potential at the proteome level. As such, a variety of mass spectrometry-based approaches and biological samples were utilized for the discovery of these potential prognostic protein markers resulting in twenty-four candidates. Upon the identification of candidate biomarkers, a mass spectrometry-based assay for the simultaneous quantification of these proteins in breast cancer tissue samples was established. The developed assay was used for measuring the relative expression levels of the potential biomarkers in a cohort of 96 breast cancer tissue samples from untreated patients with early stage breast cancer. This exercise uncovered two proteins that showed the potential to discriminate between ER-positive patients at high and low risk of disease recurrence, namely KPNA2 and CDK1.
In conclusion, the present dissertation describes the development of a preclinical exploratory study, from the discovery to the preliminary verification of potential prognostic biomarkers for breast cancer patients.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/65715 |
| Date | 13 August 2014 |
| Creators | Pavlou, Maria |
| Contributors | Diamandis, Eleftherios |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis, Dataset |
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