Data Resource Profile: thousands of circulating RNA profiles of pre-clinical samples from the Janus Serum Bank Cohort

Langseth, Hilde; Umu, Sinan Uğur; Bucher-Johannessen, Cecilie; Babigumira, Ronnie; Leithaug, Magnus; Lauritzen, Marianne; Víneis, Paolo; Ursin, Giske; Lyle, Robert; Rounge, Trine B.

doi:10.1101/2021.01.22.20243154

Cited by 3 publications

(4 citation statements)

References 28 publications

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“…Small RNA sequencing data was generated as part of the large, ongoing multi-cancer JanusRNA project ( 17 ) at the Cancer Registry of Norway (CRN). JanusRNA has its origin in the large population-based Janus Serum Bank Cohort (JSB) established in 1973 and is a population-based prospective cancer biobank including 318,628 participants with serum samples collected between 1972–2004, as previously described ( 18 , 19 ).…”

Section: Methodsmentioning

confidence: 99%

“…This resulted in the inclusion of 80 invasive ovarian cancer cases with a total of 106 samples (n=14 with two samples and n=4 with three samples or more) diagnosed up to 7 years following blood collection. A common control set for all cancers included in JanusRNA were measured together with other cancer types in the JanusRNA study ( 17 , 21 ). Due to a moderate batch effect between ovarian cases and controls discovered using principal components analysis ( Supplementary Figure 1 ), controls were discarded in this study.…”

Section: Methodsmentioning

confidence: 99%

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Validation of miRNA signatures for ovarian cancer earlier detection in the pre-diagnosis setting using machine learning approaches

Stawiski,

Fortner,

Pestarino

et al. 2024

Front. Oncol.

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IntroductionEffective strategies for early detection of epithelial ovarian cancer are lacking. We evaluated whether a panel of 14 previously established circulating microRNAs could discriminate between cases diagnosed <2 years after serum collection and those diagnosed 2–7 years after serum collection. miRNA sequencing data from subsequent ovarian cancer cases were obtained as part of the ongoing multi-cancer JanusRNA project, utilizing pre-diagnostic serum samples from the Janus Serum Bank and linked to the Cancer Registry of Norway for cancer outcomes.MethodsWe included a total of 80 ovarian cancer cases contributing 80 serum samples and compared 40 serum samples from cases with samples collected <2 years prior to diagnosis with 40 serum samples from cases with sample collection ≥2 to 7 years. We employed the extreme gradient boosting (XGBoost) algorithm to train a binary classification model using 70% of the available data, while the model was tested on the remaining 30% of the dataset.ResultsThe performance of the model was evaluated using repeated holdout validation. The previously established set of miRNAs achieved a median area under the receiver operating characteristic curve (AUC) of 0.771 in the test sets. Four out of 14 miRNAs (hsa-miR-200a-3p, hsa-miR-1246, hsa-miR-203a-3p, hsa-miR-23b-3p) exhibited higher expression levels closer to diagnosis, consistent with the previously reported upregulation in cancer cases, with statistical significance observed only for hsa-miR-200a-3p (beta=0.14; p=0.04). DiscussionThe discrimination potential of the selected models provides evidence of the robustness of the miRNA signature for ovarian cancer.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Validation of miRNA signatures for ovarian cancer earlier detection in the pre-diagnosis setting using machine learning approaches

Stawiski,

Fortner,

Pestarino

et al. 2024

Front. Oncol.

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“…En startfinansiering fra Kreftregisterets fond ga oss muligheten til å teste ut kvaliteten på Janusprøvene og optimalisere analysemetodene ("pipeline") før vi startet storskalaanalyser (8). Vi har nå gjennomført dypsekvensering av Janusprøver fra mer enn 2 700 kreftpasienter og nesten 700 kreftfrie kontrollpersoner (13). Prosjektet har senere fått ny finansiering fra både Kreftforeningen og Helse Sør-Øst.…”

Section: Tidlige Diagnostiske Markører For Kreftunclassified

Janus serumbank – jakten på biomarkører for kreft

Langseth¹,

Kymre²,

Slyngstad³

et al. 2022

Nor J Epidemiol

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Janus is a population-based prospective cancer biobank established in 1973. The biobank consists of residual blood serum samples from more than 300 000 men and women, who participated in different health surveys in Norway or as Red Cross blood donors during the period 1972–2004. It was established on the initiative of Professor of Pathology, Olav Torgersen (1907–78), referring to the longstanding maxim that ‘prevention is better than cure’. The purpose of the biobank was to build up a resource for studies of cancer aetiology and early detection of cancer, by measuring biochemical and immunological changes several years before the patient’s diagnosis. The Janus cohort, with comprehensive registry-based follow-up, enables longitudinal assessment of the preclinical stage in cancer patients or the latent period before the tumour has been established, and is ideal for the search of novel biomarkers of cancer. The Cancer Registry of Norway took over the cohort in 2004. In 2019 the biobank was moved into new semi-automated storage facilities and all samples were barcoded. The biobank is annually linked to the Cancer Registry for updates on new cancer cases and by the end of 2020 the number of incident cancer cases in Janus was 107 366. A continuous work in Janus has been on quality assurance of the biospecimens by investigating sample quality parameters like the effect of different pre-processing of the samples as well as storage time and temperature. We have investigated the stability of various hormones, proteins, metabolites, electrolytes and RNAs. This work has contributed to important knowledge in establishing Good Biobank Practice in Norway. In recent years we have also shown that the trace amounts of DNA in Janus is of sufficient quality for genotyping and methylation studies. Today Janus is used in a large number of national and international studies and is an active part in several international cancer consortia. The scientific output from the biobank contains a substantial proportion of high impact papers that have contributed to increased knowledge on cancer biomarkers for use in cancer control. Many of the projects have focused on investigating the association between infections and cancer, environmental exposures and cancer and early detection biomarkers. In recent years we have identified RNAs as early detection and potentially screening biomarkers of cancer. We have developed and optimized an RNA sequencing method for samples with low input RNA and produced RNA profiles of pre-clinical samples from 1631 cancer patients and 673 cancer-free controls. The sequencing data is combined with detailed cancer information from the Cancer Registry of Norway and information on environmental exposures from health surveys, in advanced biocomputational analysis. Results published on the healthy control group shows that RNA expression levels are significantly affected by age and smoking. For lung cancer the results showed dynamic changes in differentially expressed circulating RNAs specific to histology and stage. In the future we aim to utilize Janus in omics analyses and produce large scale datasets that can be shared and used in many research projects.

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“…In addition, 111 matched controls that were cancer-free 10 years after blood donation were also retrieved. This sample set is part of a larger data collection named JanusRNA, described in detail by Langseth., et al (33). RNA profiles were generated by extracting RNAs from 400 µl serum, and small RNA sequencing libraries were produced with NEBNext kit (Cat.…”

Section: Data and Sample Descriptionmentioning

confidence: 99%

Pre-Diagnostic Circulating RNAs Networks Identify Testicular Germ Cell Tumour Susceptibility Genes

Burton

Rounge

Haugen

et al. 2022

Preprint

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Testicular germ cell tumour (TGCT) is a malignancy with known inherited risk factors, affecting young men. We have previously identified several hundred circulating RNAs that were differentially expressed in pre-diagnostic serum samples from TGCT cases when compared to healthy controls. In this study we performed network preservation analyses of pre-diagnostic serum mRNA and miRNA. Hub genes, enriched functional pathways, and regulatory feature prediction were identified for all TGCT, seminoma, and non-seminoma cases separately, compared to controls. We identifiedUBCA1,RCC1,FMR1,OSA3, andUBE2Was hub genes associated with TGCT. The genesOSA3andUBE2Whave previously been associated with testicular dysgenesis syndrome (TDS) disorders, including hypospadias. Previously described TGCT susceptibility genesTEX14,NARS2, andG3BP2were identified as hub genes in both seminoma and non-seminoma networks. Furthermore, network module analysis showed prediction of transcription factors for oestrogen-related receptors. The overlap between network hub genes and TGCT susceptibility genes indicates a role in the progression from germ cell neoplasia in situ (GCNIS) to TGCT that should be further investigated.

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Data Resource Profile: thousands of circulating RNA profiles of pre-clinical samples from the Janus Serum Bank Cohort

Cited by 3 publications

References 28 publications

Validation of miRNA signatures for ovarian cancer earlier detection in the pre-diagnosis setting using machine learning approaches

Validation of miRNA signatures for ovarian cancer earlier detection in the pre-diagnosis setting using machine learning approaches

Janus serumbank – jakten på biomarkører for kreft

Pre-Diagnostic Circulating RNAs Networks Identify Testicular Germ Cell Tumour Susceptibility Genes

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