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Exploration of disease-specific biomarkers in cancer research by integrating biological knowledge and high throughput data

Sfakianakis Stylianos

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Summary

Breast cancer is widely known as the most common malignancy in women worldwide and presents the second highest mortality rate. In breast cancer patients, it is not the primary tumour, but its metastases at distant sites that are the main cause of death. To establish a metastasis, tumour cells enter the circulatory blood stream, arrest in capillary beds of distant organs, invade the host tissue and proliferate (Circulating Tumor Cells, CTCs). The aim of this thesis is the use of statistics and computational techniques in order to identify differences and similarities between the blood and tissue samples of cancer patients and healthy populations. Potential discoveries in this endeavor can provide answers for the molecular characterization of metastatic breast cancer and the presence of CTCs.A large compendium of publicly available gene expression data sets from DNA microarrays has been brought together and carefully merged in order to overcome technical and other variations. A number of statistical comparisons between the different in origin (blood or tissue) or in disease status (cancerous or healthy) samples yielded a small number of 27 genes («biomarkers»). These biological markers were then associated with well curated sources of biological knowledge, such as biological networks, and subjected to novel algorithmic procedures so as to establish the underlying biological foundation and to further elicit features (genes) for the supervised and unsupervised classification of breast cancer patients.

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