Research paves the way for predicting disease progression for incurable cancer

Researchers have come one step closer to answering why, in some patients, a type of lymphoma changes from indolent to aggressive, and in particular they are closer to identifying which patients are at high risk of this change happening.

Part of the answer lies in the protein expression in the tumour, explains Associate Professor Maja Ludvigsen from the Department of Clinical Medicine at Aarhus University. Maja is one of the authors of a new study on the subject, which has just been published in the scientific journal Blood Advances.

Follicular lymphoma is an incurable lymphoma. But unlike many other cancers, it is not always aggressive from the start. This means that patients with the disease have to live with the uncertainty of when - and how - the cancer will develop. It also means frequent visits to hospital to monitor any acute developments.

Patients generally respond well to treatment and most are physically well, even with the serious diagnosis. However, for the majority of patients, the disease will flare up periodically and for some patients it will change into an aggressive form.

"For some, the disease can be controlled with treatment. For others, the cancer will progress to the  aggressive lymphoma type, diffuse large B-cell lymphoma (DLBCL). This development is associated with a deterioration in the patient’s condition and the chances of survival are significantly lower," says Maja Ludvigsen.

The study was conducted by PhD student Marie Beck Hairing Enemark, and the researchers analysed the protein composition of cancerous tumours from patients with follicular lymphoma. This has provided new insights into why the cancer transforms into an aggressive type and, in particular, which patients are at high risk of being affected.

Can cause worry and anxiety

"You could consider the proteins in the tissue as the tumour's toolbox. Our study shows that tumours from patients who experience transformation to the aggressive type later in the course of the disease have a different protein content at the time of diagnosis. We can utilise this to find out more about the mechanism that drives the transformation. Interestingly, we found proteins that affect the cells' ability to survive," says Maja Ludvigsen.

"We therefore decided to take a deeper look at five proteins, and this confirmed a different level of expression in the tumour in patients with different disease progression. It is particularly interesting to note that, based on the combined expression of the five proteins, at the time of diagnosis we were able to identify patients who would later experience transformation to the aggressive lymphoma," explains the researcher. She calls the study a groundbreaking discovery about the biology of the transformation process in this type of cancer.

"At the moment, patients have to live with the uncertainty of when and how their disease will return. This can lead to high levels of worry and anxiety," says Maja Ludvigsen. She hopes that, in the future, the study can be used to predict the course of an individual patient's disease.

"This would mean that low-risk patients could be less concerned about their disease and it could save many unnecessary hospital visits. Perhaps it could even take some of the pressure off our busy hospitals. It will also be possible to tailor treatment strategies to high-risk patients earlier, ultimately with the hope of treating and saving a larger group of patients than is possible today," she says.

 Maja Ludvigsen points out that, although the researchers have validated the results in tumour tissue from patients, further research is necessary to see whether the results also apply to a larger patient group. Expansion of the study has already been initiated as part of the research project.

The research results - more information

• In a retrospective cohort study, the researchers investigated the protein profile in cancerous tumours using mass spectrometry-based proteomics analysis and immunohistochemistry (IHC) combined with digital image analysis.
• The project is a collaboration across Blood Diseases and Department of Pathology, Aarhus University Hospital and Department of Clinical Medicine, Katharina Wolter, Amanda Jessica Campbell, Maja Dam Andersen, Emma Frasez Sørensen, Trine Engelbrect Hybel, Kristina Lystlund Lauridsen, Stephen Hamiton-Dutroit and Department of Pathology at Rigshospitalet, Copenhagen, Trine Lindhart Plesner and Department of Biomedicine, Aarhus University, Bent Honoré.
• External funding: Karen Elise Jensen Foundation, Danish Lymphoma Group, Ølufgaard, A. P. Møller and Chastine Mc-Kinney Møller Foundation.
• Read more in the scientific article: https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2023011299/498309/Proteomics-identify-apoptotic-markers-as

Contact

Associate Professor Maja Ludvigsen
Aarhus University, Department of Clinical Medicine and Aarhus University Hospital, Department of Haematology
Mobile: +45 22 85 95 23
Mail: majlud@clin.au.dk