Course in methods of cancer biomarker research

This is a bi-annual 5-ECTS course in the CCBIO Research School for Cancer Studies, equipped to provide an understanding of the various methodologies and their application in basic and translational cancer research.

A broad range of expertise

Lars A. Akslen gave an introductory talk on precision medicine and companion diagnostics for patient stratification, covering definitions and historical development of concepts and clinical development. Elisabeth Ognedal explained the basics of nucleotides and methods to study nucleotide-based biomarkers, and Manuel Carrasco gave an overview of techniques to study protein-based biomarkers. Erling A. Hoivik presented epigenetics and miRNA, and Vandana Ardawatia gave an introduction to the immunohistochemistry protocol and the importance of standardization. Carina Strell introduced proximity ligation assay with inspirational examples from her biomarker research where she aims to explore the technology to detect active immune checkpoint signaling as a novel concept of functional diagnostics for better prediction of immunotherapy efficacy. Preclinical research models were taught by Heidrun Vethe who talked about organoids, and Katrin Kleinmanns gave a talk on the evolution of ever more advanced animal models, and in particular immune-competent models, to better model human cancer development and therapy response. Kenneth Finne taught the students about laser microdissection and introduced low- and high-resolution proteomics. Kristin Dahl-Michelsen showed the possibilities of Nanostring technology and the application of the Prosigna test to evaluate the risk of recurrence of breast cancer, based on the 50-gene expression profile. Olav Vintermyr gave a great overview of the development of Next Generation Sequencing (NGS) technology. Elisabeth Wik and Erling A. Hoivik held a very interesting and interactive session where they discussed the hallmarks of an ideal biomarker, addressed several challenges in the field of cancer biomarker research, and reflected on how to better bridge the gaps from the explorative attempts to improve patient stratification to actual clinical implementation. 

Oddmund Nordgård (UiS), normally based in Stavanger, came to Bergen to talk about liquid biopsies and the detection of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), and extracellular vesicles in various body fluids. Nordgård explained the technical development in the field as well as promising clinical applications, including work from his research group showing that comprehensive ctDNA measurements in advanced pancreatic ductal adenocarcinoma improve prediction of clinical outcomes and enable dynamic tracking of disease progression. 

AI and data resources

Marit Valla (NTNU) joined us from Trondheim to give the students an introduction to machine learning and artificial intelligence (AI). Marit Valla focused on the use of AI in pathology, and she introduced Fast Pathology, an open-source platform for deep learning-based research and decision support in digital pathology created by Valla and colleagues at SINTEF and NTNU. Valla also gave a well-attended CCBIO Seminar on Thursday, September 26 with further examples. In her talk, Valla mainly focused on the use of artificial intelligence (AI) in pathology. She presented research results within digital pathology and AI analysis in breast and lung cancer and showed examples of AI-based image analysis in other fields of medicine. 
 
Ann Cathrine Kroksveen gave a very useful introduction to biobanking and the associated regulations and practicalities. Ingeborg Winge, formerly a member of CCBIO and Lars A. Akslen’s lab, presented ELIXIR, her new workplace and an intergovernmental organization that brings together life science resources from across Europe, such as databases, software tools, training materials, cloud storage, and supercomputers.

Emphasis on spatial omics analysis

Emphasis was placed on spatial omics techniques; first out was Carina Strell who gave an interesting lecture on in situ sequencing technology and spatial omics analysis. After an introduction to the topic of flow cytometry and mass cytometry by Jørn Skavland, Vladan Milosevic and Kenneth Finne gave introductions to the Hyperion Imaging Mass Cytometry (IMC) technology and continued by covering in-depth practical considerations and data analysis. Senior bioinformatician Dimitrios Kleftogiannis further covered the development and application of computational approaches to analyze IMC data and the integration of machine learning approaches to enable users to answer biological questions of interest in their biomarker research. The session on IMC and data analysis was particularly well received by the students who already apply mass cytometry or IMC technology in their research projects, and this sparked an interest in the technology amongst the students not yet familiar with the technology. 

Critical thinking and evaluation

In the closing of the course, Oddbjørn Straume engaged the students with an interactive session discussing a clinical case, where the students were challenged to show the application of the knowledge acquired over the three course days. The portfolio assessment of the students claiming ECTS credits for the course consisted of presentations of group work and an exam. A highlight of the course was the student presentations on the final day, where the students critically evaluated a research paper that was assigned to them by an expert panel. Cornelia Schuster, Heidrun Vethe, and Katrin Kleinmanns did a comprehensive job of evaluating the student presentations. 

Thanks to all the expert lecturers

Academic responsibility for this course is held by Lars A. Akslen and Agnete S. T. Engelsen. The course coordinators this year were Manuel Carrasco Fernandez and Tessa Lohr.  Organizers Akslen and Engelsen want to send a special thanks to Manuel Carrasco Fernandez for his assistance during the three intense course days on campus and to all the expert lecturers for offering their valuable time to engage, challenge, and inspire the attending PhD students. 

“The students are extremely fortunate to have this great line-up of experts sharing their knowledge on cancer biomarker research and methods, and we believe most students appreciated the opportunity to learn from the best,” Engelsen concludes.