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Title: Breast cancer biomarker discovery
Author: Zeidan, Bashar
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2013
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Several environmental and genetic factors are involved in breast cancer development and prognosis. It is clear that mortality rate of breast and other cancers increase with advanced clinical and pathological stage. Early detection thus holds the best cure and identification of prospective markers for breast cancer early detection, as well as understanding the mechanisms of its tumourigenesis and metastatic spread are prerequisites for more effective disease management. This report describes our investigations in breast cancer biomarkers discovery. Here, serum samples from healthy volunteers and patients with breast tumours were analysed and compared to reveal diagnostic and prognostic breast cancer biomarkers. Biobanks hold a large number of samples that could provide statistically powerful cohorts with a wealth of lengthy follow up data; useful for pre disease / treatment biomarker discovery. However, ambiguous handling standards and source variability have limited their analysis. Conducting a two centre study, we illustrated that archival serum samples can be reliably analysed with high reproducibility. This highlights the utility of such samples for validation of markers discovered in recent studies. In addition, these samples could select for "real world" biologically stable marker entities. This work suggested that this is a potentially useful proteomic arena; however the corner stone for any future archival discovery projects remains dependent on multi centre immunovalidation. Breast cancer biomarkers including ER/PR and HER2 status; have led to targeted patient stratification and therapy. A more complex molecular sub classification could explain the different outcome within the disease sub groups. However, clinically reliable early detection and markers remain missing . Here, we investigated differentially expressed serum markers between non metastatic breast cancer, benign breast disease and healthy volunteers. Three validated candidate biomarkers (ANX A3, Apo Cl and a 6.4kDa biomarker) differentiating the three groups. Such breast cancer markers can be used as adjuncts to mammography. Further validation of these markers is ongoing and will be followed by elucidation of potential related molecular pathways. Finally, using a novel proteomic profiling platform, we identified and validated three prediction markers of post treatment outcome in early onset breast cancer. Here, ANX A2, Apo Cl and NOS2 were confirmed as serum prognosticators, and further validation and elucidation of their biological role in the disease holds promise for improved and personalised treatment regimes.
Supervisor: Townsend, Paul A. ; Packham, Graham Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH426 Genetics ; RC0254 Neoplasms. Tumors. Oncology (including Cancer)