Professor Claus Lindbjerg Andersen, Department of Molecular Medicine, Aarhus University Hospital, Denmark.

Researchers from Aarhus University Hospital and Aarhus University in Denmark have invented a molecular method to detect aggressive colorectal cancer that does not require costly collection of additional tissue samples from each patient. Potentially, this allows a higher number of patients with colorectal cancer to be analysed molecularly to help identify those with particular aggressive cancer.

Colorectal cancer is one of the most fatal types of cancer in the world. Although about two-thirds of patients are treated with curative intent, about one-third will experience recurrence of disease.

To reduce the number of fatalities, it is crucial that patients with aggressive disease are identified as soon as possible and offered extra treatment to reduce their risk of recurrence. Previous research has shown that dividing colorectal cancer into so-called molecular sub-types can improve the prediction of recurrence risk. However, this promising molecular strategy is not immediately suitable in clinical practice as it requires costly, additional collection of tissue samples from each patient.

New results from a large study by researchers from Department of Molecular Medicine at Aarhus University Hospital have now shown how colorectal cancer subtypes and aggressiveness can be identified by using the tissue samples that are already standardly collected from all patients. In this way, it has now become feasible to analyse all patients for presence of aggressive cancer and adapt their treatment accordingly.

Analysis of more robust molecules 

- The current methods to analyse cancer molecular subtypes and aggressiveness are based on profiling of so-called RNA molecules. Unfortunately, RNA molecules are fragile and therefore partly degraded in the tissue samples that are standardly collected in the clinic. Our strategy was therefore to develop a method that instead rely on analysis of DNA, which is more stable, says associate professor Jesper Bertram Bramsen from Department of Molecular Medicine, who has played a leading role in the project.

- Our method shows that you can obtain information about cancer RNA expression, molecular subtype and aggressiveness from DNA analysis to much a greater extent than we initially thought. Therefore, analysis of the robust DNA molecule may now replace RNA analyses, Jesper Bertram Bramsen continues.

The method also makes it possible to perform molecular analyses using archival samples from existing biobanks, which improves the possibility to develop new cancer biomarkers in the future.

- For a long time, we have wanted to be able to perform comprehensive molecular analyses of archived cancer samples. Using archival samples, it will be possible to focus and optimize the development of new biomarkers that are e.g. specific for molecular sub-types or predicts a patients’ response to a particular treatment. We are looking forward to use our new method in these types of projects, says Professor Claus Lindberg Andersen, head of the research group at Department of Molecular Medicine.

Molecular analysis for a higher number of patients

In this study, researchers analysed more than 800 colorectal cancer samples and confirmed that the DNA-based method can work better than RNA-based methods in clinical and archival tissue samples.

- It would be a huge step forward, if molecular predictions could be used more broadly in patient treatment, which has been difficult so far due to the fragility of RNA. E.g., patients with aggressive disease could be treated more intensively while other patients could receive less intensive treatment with fewer side effects. That is why we have specifically tailored our molecular method for the clinical sample types that are already available from all patients, Claus Lindbjerg Andersen adds.

The researchers also predict that the method will be adaptable to predict the treatment response of e.g. chemotherapy and immune therapy, which are next critical steps to optimise follow-up treatment of patients with colorectal cancer.

- We are now working intensively to further develop the method in order to test it in practice as a new molecular tool in the planning of treatment for patients with colorectal cancer, professor Claus Lindbjerg Andersen concludes.

Behing the research result:

Study type: Molecular profiling and classification, basic research, retrospective cohort

Collaborators: Josep Carreras Leukaemia Research Institute (IJC), Barcelona, Spain

External financing: The research is supported by the EU FP7 project SYSCOL (UE7-SYSCOL-258236), Novo Nordisk fundation, (NNF16OC0023182), Det Frie Forskningsråd (DFF - 0602-02128B, DFF – 4183-00619, DFF - 7016-00332B), NEYE foundation, Danish Cancer Research foundation (DKF-2017-26 - (26) and Aage og Johanne Louis-Hansens Fond (17-2-0457).

Conflicts of interest: none

Link to original article:

Resultats are published in the internationally acknowledge journal Nature Communications:

MethCORR modelling of methylomes from formalin-fixed paraffin-embedded tissue enables characterization and prognostication of colorectal cancer

Trine B. Mattesen, Mads H. Rasmussen, Juan Sandoval, Halit Ongen, Sigrid S. Árnadóttir, Josephine Gladov, Anna Martinez-Cardus, Manuel Castro de Moura, Anders H. Madsen, Søren Laurberg, Emmanouil T. Dermitzakis, Manel Esteller, Claus L. Andersen & Jesper B. Bramsen

Further information:

Professor Claus Lindbjerg Andersen, Department of Molecular Medicine, Aarhus University Hospital, Denmark and Department of Clinical Medicine, Aarhus University, Denmark

Tel.: +45 78 45 53 19