From left: Robert Lyle, Trine Rounge, Magnus Leithaug, Hilde Langseth, Sinan Ugur Umu, Marianne Lauritzen and Cecilie Bucher-Johannessen
Serum contain many types of RNA molecules such as protein-coding messenger RNAs (mRNAs), miRNAs, piRNAs, transfer RNAs (tRNAs) and other non-coding RNA molecules. Regulatory RNAs have been implicated in cancer and many other diseases and are thus promising biomarkers of cancer.
We have initiated and are leading several large projects studying RNA as cancer biomarkers and RNAs role in cancer development. We have a close collaboration with the Norwegian Sequencing Center (NSC) at Oslo University Hospital (OUS), bioinformatics core facilities at the University of Oslo and several . In addition, several international collaborators are involved in this project.
Our study uses pre-diagnostic samples from the large population-based Janus Serum Bank, the Cancer Registry detailed information on cancer diagnosis, and epidemiological data from national health surveys. This provides us with a unique dataset to investigate early biomarkers of cancer.
This project is financed by the Research Council of Norway, Norwegian Cancer Society and EU Horizon 2020.
Annually, about 34,000 Norwegians are diagnosed with cancer and it is the leading cause of death in Norway.
Colon cancer is one of the most common cancer types in Norway and the number of yearly diagnosis has increased rapidly since the 1960s for both men and women. Symptoms of colon cancer often occurs at a late stage, when prognosis is uncertain or poor.
Similarly, lung cancer is the most common cause of cancer death for both men and women. Even though the number of smokers are declining, the yearly occurrences are still increasing. Due to lack of efficient strategies for screening or early diagnosis, the prognosis is generally poor.
Prostate and breast cancers are the most frequently occurring cancer types among men and women, respectively and accounts for 30% of all cancer cases.
Cancer survival depends on how early the disease is diagnosed and treatment can commence. For further key numbers from the Norwegian Cancer Registry: https://www.kreftregisteret.no/Registrene/Kreft_i_Norge/
Aim of research
The overall research aim is to discover RNAs as early detection biomarkers of cancer. The long-term goal is to exploit such biomarkers in cancer screening.
We have produced RNA expression profiles from more than 2000 cancer cases and 600 healthy controls using pre-diagnostic serum samples from the Janus Serum Bank, on an Illumina HiSeq platform at NSC. We have reached an average sequence depth of 18 million sequences, and identified more than 600 unique miRNAs per sample in addition to other noncoding RNAs.
Our data set contain quality assured expression profiles, and we are currently working on making them accessible by national and international research groups.
Overview of ongoing Projects
Genome-wide miRNA profiling in prediagnostic samples from Janus Serum Bank for early diagnosis, improved therapy & surveillance of cancer
Biomarkers of Cancer: Biocomputional analysis of data from population-based biobanks and health registries
Genetic susceptibility to testicular cancer
miRNA signatures in patients with colon cancer, breast cancer and lung cancer
EULAT Eradicate Gallbladder cancer – funded by Horizon2020
Prediagnostic dynamics of small non-coding RNAs and genetic variants in the causal estimation of endometrial cancer
PREDICT: the Prospective Early Detection Consortium for ovarian cancer
Core Facility Leader, Robert Lyle, PhD
Lab Technician, Magnus Leithaug, BSc
Chair of 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 Oncology, Assoc. Prof Åslaug Helland, MD, PhD
OsloMet – storbyuniversitetet
Faculty of Health Sciences, Trine B. Haugen, PhD
University of Heidelberg
Department of Biometry and Informatics, Prof. Justo Lorenzo Bermejo, PhD
German Cancer Research Centre
Division of Cancer Epidemiology, Prof. Rudolf Kaaks, PhD
Division of Cancer Epidemiology, Renée Fortner, PhD
Harvard Medical School
Brigham And Women’s Hospital, Prof. Kevin Elias, MD
School of Public Health, Imperial College London
Chair of Environmental Epidemiology, Prof. Paolo Vineis, MD, MPH, FFPH
Epidemiology & Biostatistics, Verena Züber, PhD
Epidemiology & Biostatistics, Marc Chadeu, PhD
How to get access to data
All research projects that includes information and/or biological material from Janus Serum Bank must comply with the EU’s General Data Protection Regulation (GDPR). This means that the processing must have approval from the Regional Committee for Medical Research in Norway (REC). Furthermore the processing needs legal basis according to GDPR Article 6 and 9. The applicant must have considered the need for a Data Protection Impact Assessment (DPIA) according to GDPR article 35. The applicant must prove that these requirements have been met before the data can be made available. Disclosure of information and/or biological material to countries outside the EU requires that the conditions in GDPR are met. For more information email miRJanus[a]kreftregisteret.no.
Andreas Keller , Tobias Fehlmann , Christina Backes , Fabian Kern , Randi Gislefoss , Hilde Langseth , Trine B. Rounge , Nicole Ludwig & Eckart Meese, 2020. "Competitive learning suggests circulating miRNA profiles for cancers decades prior to diagnosis".
Umu SU, Langseth H, Keller A, Meese E, Helland Å, Lyle R, Rounge TB, 2019. "A 10 year prediagnostic followup study shows that serum RNA signals are highly dynamic in lung carcinogenesis"
Rounge TB, Umu SU, Lyle R, Langseth H, et al 2018. "Circulating small non-coding RNAs associated with age, sex, smoking, body mass and physical activity".
Umu SU, Langseth H, Bucher-Johannessen C, Lauritzen M, Leithaug M, Lyle R, Rounge TB, et al 2017. "A comprehensive profile of circulating RNAs in human serum"
Fehlmann T, Langseth H, Rounge TB, Umu SU, et al 2017. "A high-resolution map of the human small non-coding transcriptome".
Keller A, Rounge TB, Langseth H, et al 2017. "Sources to variability in circulating human miRNA signatures".
Rounge TB, Langseth H, Lauritzen M, et al. 2015. "microRNA Biomarker Discovery and High-Throughput DNA Sequencing Are Possible Using Long-term Archived Serum Samples".
Keller A, Langseth H, et al. 2011. "Stable serum miRNA profiles as potential tool for non-invasive lung cancer diagnosis".