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Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Ananya Choudhury, Manchester University, United Kingdom
- Second opponent: Associate Professor May-Britt Tessem, NTNU - Norwegian University of Science and Technology, Norway
- Third member and chair of the evaluation committee: Professor II Jørgen Wesche, Faculty of Medicine, University of Oslo
Chair of the Defence
Professor II Kjersti Flatmark, University of Oslo
Principal Supervisor
Scientist Heidi Lyng, Department of Radiation Biology, Oslo University Hospital
Summary
The severity of prostate cancer spans from insignificant to life-threatening. To ensure optimal treatment of each patient, it is important to predict the disease aggressiveness. This can prevent over-treatment of indolent cancers or that aggressive cancers are overseen.
The overall aim of this thesis was to explore biopsy- and imaging-based biomarkers for detection of aggressive disease among prostate cancer patients.
Hypoxia is an adverse factor for prostate cancer. In this work, a previously published hypoxia gene signature was shown to reflect hypoxia in the entire tumor lesion, and not just where the tissue biopsy was obtained from. The gene signature also showed prognostic potential in external patient cohorts. Biomarkers measured in blood provide lower risk of infection, and repeated measurements are more feasible. MicroRNAs are regulators of gene expression and may be easier to detect in blood as compared to genes. Two microRNA-based signatures reflecting hypoxia were discovered, both showing prognostic potential in external patent cohorts.
Medical images are valuable for detection of biomarkers, but an understanding of the connection between image parameters and the underlying biology is important. In the work of this thesis, an MRI parameter reflecting cell density was found to be associated with downregulation of the PTEN tumor suppressor gene, which is a frequent characteristic of aggressive prostate cancer. In the last study, the uptake mechanism of the FACBC PET tracer was studied. Previous preclinical studies have suggested that selected amino acid transporters are involved. However, the present study in patients shows that the uptake mechanism is far more complex.
The work included in this thesis, has provided an increased understanding of biopsy- and imaging-based biomarkers in prostate cancer. This is useful both for development of new biomarkers, but also for refinement of existing ones.
Additional information
Contact the research support staff.