Genome-wide miRNA profiling in prediagnostic samples from Janus Serum Bank for early diagnosis, improved therapy & surveillance of cancer

About 30 000 Norwegians are diagnosed with cancer annually and cancer is the second leading cause of death overall in Norway. Colorectal cancer is one of the most common cancer sites and has increased rapidly in Norway since the 1960s in both men and women. Symptoms from colon cancer often appear at a late stage, when the prognosis is uncertain or poor. Lung cancer is the predominant cause of cancer-related death in men and women, and incidence rates among women are still increasing. Due to a lack of efficient strategies for screening or early diagnosis, the prognosis is generally poor. The aim of the present study is to investigate miRNAs as early markers and potential screening biomarkers of these two cancers. miRNAs are non-coding RNAs found to play a central role in the development and course of cancer disease. We have produced high-throughput genome-wide miRNA expression profiling analyses by deep miRNA sequencing in a large set of colorectal and lung cancer cases and controls from the Janus Serum Bank. We have produced quality assured miRNA expression profiles from the raw sequencing data and will organize the accessibility of the data from the large scale analyses to national and international research groups. We have reached an average sequence depth of 18 million sequences, and identified more than 600 unique miRNA's per sample. The project is initiated by the Cancer Registry of Norway and will be performed in collaboration with Norwegian Sequencing Centre at Oslo University Hospital, bioinformatics core facility at the University of Oslo, a number of national basic science as well as clinical research groups that treat colorectal and lung cancer patients, as well as international miRNA experts in Europa and US.

Success in cancer management depends on timely detection, diagnostic precision, and optimal treatment and follow-up. In the present study we will investigate the usefulness of miRNA expression profiles as early markers of cancer. Our focus will be on col orectal and lung cancer that represent great public health concerns, and where there is a potentially large impact of early detection and treatment. We aim to identify miRNA expression profiles associated with these two cancer forms, both overall, as well as for subtypes defined by topography, morphology and stage. The study has a nested case-cohort design, where cases and controls are selected among the Janus Serumbank cohort members. We restrict our analyses to cancer patients with samples collected wi thin 10 years prior to diagnosis, divided in three lag-time groups; < 1 year, 1-4 years and 5-10 years. This constitutes 1452 samples from 1021 cancer cases indicating that multiple samples are available from a large proportion of the cases, giving the op portunity to investigate temporal variations in samples from the same individual. The sample material represents specimens from 363 colon cancer patients, 203 patients with rectal cancer and 455 patients with lung cancer. To compare miRNA expression profi les in colorectal and lung cancer patients and healthy individuals, we will select a subcohort of 455 healthy Janus participants. We will obtain high-throughput genome-wide miRNA expression profiling analyses by conducting deep miRNA sequencing using the genomic core facilities at the Norwegian Sequencing Centre at Oslo University Hospital. We will produce quality assured miRNA expression profiles from the raw sequencing data in collaboration with the bioinformatics core facility at the University of Oslo . The data will be used to identify early detection biomarkers for these two cancers. We will make the data accessible for large scale analyses to national and international research groups.