JanusRNA - identification of early cancer biomarkers

RNA are involved in numerous cellular processes in cancer development. We are currently investigating RNA as early detection and potential screening biomarkers of cancer.
Last updated: 9/8/2020

From left: Robert Lyle, Trine Rounge, Magnus Leithaug, Hilde Langseth, Sinan Ugur Umu, Marianne Lauritzen and Cecilie Bucher-Johannessen 

 

Project summary

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.

Background

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.

Data

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.

Figure 1: Overall classification of the mapped reads in serum samples from cancer-free individuals (Umu et al. 2018).
Figure 2: The number of RNAs that can be related to lung cancer development varies in the decade before diagnosis (Umu et al. 2019).

 

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

Collaborators

Norwegian Sequencing Centre:

Core Facility Leader, Robert Lyle, PhD

Lab Technician, Magnus Leithaug, BSc

 

 

Saarland University:

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

zurück zur Startseite

 

German Cancer Research Centre

Division of Cancer Epidemiology, Prof. Rudolf Kaaks, PhD

Division of Cancer Epidemiology, Renée Fortner, PhD

Deutsches Krebsforschungszentrum

 

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.

Publications

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".

Published: 24.08.2017