Trial lecture: Circulating cell-free RNA in early detection of cancer: current methodologies and challenges.
Ordinary opponents:
- First opponent: Senior Scientist Kristian Almstrup, Department of Growth and Reproduction, National Hospital, Denmark
- Second opponent: Professor Ole Christian Lingjærde, University of Oslo
- Leader of the committee: Associate Professor Viola Lobert, OsloMet
Leader of the public defence is Professor Rune Andreassen, OsloMet.
The main supervisor is Professor Trine B. Haugen, OsloMet. The co-supervisor: Professor Trine B. Rounge, University of Oslo.
Thesis abstract
Although rare, testicular germ cell tumour (TGCT) is the most common cancer type in young males and has shown an increasingly high incidence rate in the last decades, especially in Nordic countries. TGCT originates in foetal life and can be categorised into two subtypes, non-seminomas and seminomas.
The aetiology behind the disease is mainly unknown, but both genetic and environmental factors may play a role. Approximately 80 susceptibility genes have so far identified.
The disease is highly curable due to effective treatment and follow-up. However, the treatment may lead to late-effects, and it is of importance to identify biomarkers in the time period before diagnosis to initiate the treatment as early as possible. Non-coding RNA has been shown to be potential biomarkers for various diseases, and in this project, we investigated the RNA profile in serum from persons that later developed TGCT.
Main research findings
The serum samples had previously been collected in a biobank, the Janus Serum Bank, and the pre-diagnostic period in this study was up to 10 years. By using bioinformatics, we found that multiple types of small non-coding RNAs were expressed differentially between patients who developed TGCT and a control group.
The RNA profiles were dependent on the time before diagnosis as well as histology. However, the overall RNA profile patterns were stable between time intervals during the 10 year period. We further identified networks of related genes in the same dataset using a network correlation analysis. This revealed differences between TGCT cases and controls as well as between histological states.
We identified both known TGCT susceptibility genes, and other genes, which had previously seen as differentially expressed in TGCT patients compared to controls. Our results suggest that TGCT signals could be present earlier than the manifestation of the tumour. Furthermore, we identified genes that could play an important role in the progression from pre-malignancy to the malignant tumour.
A finding of the study was also that the fertility-related gene TEX101 was differentially expressed between cases and controls. Since there is an association between TGCT and subfertility, we searched in literature and databases to find studies that could throw light on a possible role of TEX101 as a link between the conditions.
We also looked at genes interacting in the network of TEX101. This review showed that TEX101 as well as other genes with similar functions could explain some of the aetiology between TGCT and male subfertility. It also provided insights into how the immune system may be involved in the tumour development.
For future studies, the use of multiomics, especially proteomics, would be important tools for investigating gene-protein interactions of importance for both normal and pathological testicular developments.
