Biomarkers of Cancer: Biocomputional analysis of data from population-based biobanks and health registries
Project summary
Background
Little is known about circulating miRNA expression prior to cancer diagnosis. The dynamics of differential miRNA expression with regards to cancer onset and progression are undetermined. We propose to profile miRNA expression dynamics in order to determine when, relative to diagnosis, and with what confidence, carcinogenesis can be detected.
Most studies on miRNA and cancer have shown differential miRNA expression in tissue samples collected at time of diagnosis, and several promising diagnostic miRNA biomarkers have been identified. However, also these studies have typically been small, with 10-100 patientsThese results support the idea that serum-derived miRNAs can be valuable biomarkers of cancer. Studies on circulating miRNA have so far been small, often with less than 100 patients. No study, that we are aware of, has had the statistical power to identify differentially expressed circulating miRNA and produce an in-depth understanding of circulating miRNA in context of different subtypes and aggressiveness of the cancer. However, circulating miRNA at the time of diagnosis, selectively released by malignant cells, can differentiate between cancer and healthy controls3 . In this proposal, with substantially larger sample size, we will evaluate and expand on these results.
Project aims
- Build biocomputational expertise to handle large scale biomarker and exposure data
- Assess the significance of small non-coding RNAs as early biomarkers of cancer
- Model the relationship between biomarkers, exposure and cancer occurrence
- Explore the translational potential of biomarkers of cancer
WP 1 Project management, coordination and ethical, legal and social aspects (ELSA) WP leader: Langseth Co-leaders: Ursin, Weiderpass Co-investigators: Andreassen, Gislefoss, Rounge and in addition for ELSA: Olav and Solberg
Overall aims: • Ensure that the project is managed efficiently and according to all applicable laws • Further develop common national and international ELSA standards in biobank and registry based research
WP 2 small non-coding RNA as early detection biomarkers of cancer WP leader: Rounge, co-leader: Andreassen, Co-investigators: 2 postdocs, Frigessi, Gislefoss, Grimsrud, Grotmol, Hovig, Kjærheim, Langseth, Leidinger, Lyle, Meese, Nothnagel, Stram, Tretli, Ursin,Vos, Weiderpass
Overall aim: Evaluate small non-coding RNAs as early detection biomarkers of cancer
WP 3 Environmental exposures and biomarkers of cancer WP leader Langseth Co leader Andreassen Co-investigators: 1 post doc, Frigessi, Gislefoss, Grimsrud, Kjærheim, Nothnagel, Rounge, Stram, Tretli, Ursin, Weiderpass
Aims: • Investigate the effect of exposure data from health surveys on all cancers and subtype specific cancer risk in the entire Janus cohort (~70000 cancer cases, 300000 individuals in total). • Investigate the role of the following on miRNA expression levels (~3000 cases LC, CRC, BC, PC, TGCT): 1) Exposure data from health surveys 2) Existing biomarkers from earlier research projects in the Janus cohort • Model the complex interplay between miRNA expression and environmental risk factors with respect to cancer
Publications
To be published: Ugur Umu et al., 2017. A comprehensive profile of circulating RNAs in human serum.
Collaborators
Director Giske Ursin, Phd, MD
Randi Gislefoss, PhD
Core Facility Leader, Robert Lyle, PhD
Lab Technician, Magnus Leithaug, BSc
Saarland University:
Chair for Clinical Bioinformatics, Andreas Keller, PhD
Institute of Human Genetics, Eckart Meese, PhD
Institute for Cancer Research at Oslo University Hospital:
Department of Tumor Biology and Bioinformatics Core Facility, Prof. Eivind Hovig, PhD
Department of Molecular Oncology, Prof. Ragnhild A. Lothe, PhD
Department of Oncology, Assoc. Prof Åslaug Helland, MD
Institute for Cancer Research, Bastian Fromm, PhD, Post Doc
Oslo and Akershus University College of Applied Sciences
Faculty of Health Sciences, Trine B. Haugen
University of Heidelberg
Department of Biometry and Informatics, Prof. Justo Lorenzo Bermejo, PhD
Karolinska Institutet
Department of Medical Epidemiology and Biostatistics, Prof. Fredrik Wiklund
Core Facility Leader, Robert Lyle, PhD
Lab Technician, Magnus Leithaug, BSc
Saarland University:
Chair for Clinical Bioinformatics, Andreas Keller, PhD
Institute of Human Genetics, Eckart Meese, PhD
Institute for Cancer Research at Oslo University Hospital:
Department of Tumor Biology and Bioinformatics Core Facility, Prof. Eivind Hovig, PhD
Department of Molecular Oncology, Prof. Ragnhild A. Lothe, PhD
Department of Oncology, Assoc. Prof Åslaug Helland, MD
Institute for Cancer Research, Bastian Fromm, PhD, Post Doc
Oslo and Akershus University College of Applied Sciences
Faculty of Health Sciences, Trine B. Haugen
University of Heidelberg
Department of Biometry and Informatics, Prof. Justo Lorenzo Bermejo, PhD
Karolinska Institutet
Department of Medical Epidemiology and Biostatistics, Prof. Fredrik Wiklund
Giske Ursin, Cancer Registry, Norway
Randi Gislefoss, Cancer Registry, Norway
Prof Meese and Dr. Leidinger, Institute of Human Genetics, Saarland University, Germany
Assoc. prof. Wiklund at Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet, Sweden and Prof Daniel Stram, University of Southern California
Prof. Nothnagel heads the department of Statistical Genetics and Bioinformatics at the Cologne Center of Genomics (CCG) at the University of Cologne, Germany
Institute for Molecular Medicine Finland (FIMM) technology laboratory, Helsinki, Finland
