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: Principal Investigator Andrew Erickson, University of Helsinki,
- Second opponent: Researcher Maria Karoline Andersen, Norwegian University of Science and Technology,
- Third member and chair of the evaluation committee: Associate Professor Stig Müller, Universitetet i Oslo
Chair of the Defence
Professor II Hege Elisabeth Giercksky Russnes, University of Oslo
Principal Supervisor
Professor II Rolf Inge Skotheim, University of Oslo
Summary
Prostate cancer has varying clinical outcome, where some patients have a highly aggressive disease and others have a relatively indolent cancer. Tissue-based molecular biomarkers may serve as a tool to help separate prostate cancers of different aggressiveness, but identification of optimal biomarkers is challenging due to patients often having multiple organ-confined tumours at the time of diagnosis. Further complicating the biomarker research, spatial heterogeneity within and between different tumours is common.
The thesis aimed to evaluate the previously proposed prognostic biomarkers SCHLAP1 and ERG while accounting for spatial heterogeneity, and also to analyse the transcript structures of known and novel biomarkers. The work included analysis of multiple tissue samples from each patient, with the use of a biobank and database with extensive clinical and follow-up data, and methods such as real-time RT-PCR and long-read RNA sequencing.
We found that the biomarkers were heterogeneously expressed both within the same tumour and across different tumours in 56% and 73% of patients (SCHLAP1), and 29% and 33% of patients (ERG protein), respectively. Nevertheless, when the intrapatient heterogeneity is accounted for, SCHLAP1 and ERG protein are independent prognostic biomarkers associated with biochemical recurrence.
Transcript variants of the genes ERG and ETV1 were investigated. They were heterogeneously expressed both within and between tumours in more than 90% of patients. We found that a fusion involving either gene was indicative of specific transcript variants. Moreover, a novel fusion transcript, ENSG00000284512-CMC2, was identified.
In conclusion, ERG and SCHLAP1 are robust prognostic biomarkers when spatial intrapatient heterogeneity is taken into account. The transcript variants of ERG and ETV1 are highly heterogeneously expressed within patients, and a fusion involving either gene is associated with a distinct transcript variant profile.
Additional information
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