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 Nora Cazzagon, University of Padova,
- Second opponent: Professor Per Stål, Karolinska Institutet,
- Third member and chair of the evaluation committee: Professor Hege G. Russnes, University of Oslo
Chair of the Defence
Professor Marte Høivik, University of Oslo
Principal Supervisor
Associate professor Trine Folseraas, University of Oslo
Summary
Primary sclerosing cholangitis (PSC) is a chronic liver disease that greatly increases the risk of developing biliary tract cancer. These cancers are often diagnosed late, partly because symptoms overlap with those of PSC and partly because current biochemical and imaging-based surveillance has limited sensitivity. Most patients are therefore diagnosed at a stage where curative treatment is no longer available. There is a strong need for better tools that can detect cancer earlier and guide more personalised treatment.
This thesis combines genetic analyses of tumour tissue with molecular profiling of bile to improve early detection and identify features that may open the door to targeted therapies. Whole exome sequencing of PSC-related tumours showed that this cancer subtype has a distinct molecular profile, including alterations not previously linked to biliary tract cancer. The work further identified alterations in genes that are already targets for existing cancer drugs, suggesting future therapeutic potential for selected patients.
The thesis also explored bile as a diagnostic fluid. DNA from bile showed specific methylation patterns that distinguished cancer from non-cancer in PSC with very high accuracy, and these markers may detect cancer months before current methods. In addition, protein analyses of extracellular vesicles in bile identified protein combinations that could both signal early-stage cancer and indicate which patients are at increased short-term risk of developing it.
Together, these findings highlight new molecular characteristics of PSC-related biliary tract cancer and demonstrate that bile-based biomarkers may offer more sensitive and earlier detection than today’s tools.
Additional information
Contact the research support staff.