IARC 60th Anniversary - 19-21 May 2026
Session : 19/05/26 - Posters
Hunting for pre-cancer RNA signals for early detection and improved survival – the JanusRNA study in Norway
LANGSETH H. 1,7, FORTNER R. 1,2, ROSTAMI S. 1,4, PESTARINO L. 1,3, ROUNGE T. 5,6
1 Research Department Cancer Registry of Norway at Norwegian Institute of Public Health , Oslo, Norway; 2 Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany; 3 Section for Gynecological oncology, Department of Surgical Oncology, Oslo University Hospital, Oslo, Norway; 4 Department of Paediatric Research, Department of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; 5 Bioinformatics in Life Science, Department of Pharmacy, University of Oslo, Oslo, Norway; 6 Department for Colorectal Cancer Screening, Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway; 7 Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
Background
About 39 000 Norwegians are diagnosed with cancer annually and cancer is the leading cause of death in Norway. The survival of most cancers is dependent on the stage at diagnosis. Tools to detect cancer at an early stage and improve survival are of high importance.
Objectives
The overall aim of this project is to investigate microRNA and other circulating RNAs as early biomarkers for cancer.
Methods
We produced RNA sequencing data from pre-diagnostic serum samples from the Janus Serum Bank including patients with cancer of the lung (n=404), colon (n=305) rectum (n=190), breast (n=205), prostate (n=326), ovary (n=80), testis (n=80) and gallbladder (n=27) with a sample collected within 10 years prior to diagnosis, and a frequency matched control group of 673 cancer-free individuals up to 10 years after blood collection. Also, we have produced data from endometrial cancer patents and matched controls (n=320/320).
Results
We identified differentially expressed miRNAs, isomiRs, and small nuclear RNAs between endometrial cancer (EC) cases and controls. The top miRNAs were among others miR-155-5p, miR-200b-3p, miR-589-5p, miR-151a-5p, and miR-543.We observed 47, 41, and 32 differently expressed miRNAs for EC interacting with BMI, smoking status, and physical activity, respectively, including two miRNAs (miR-223-3p and miR-29b-3p) interacting with all three factors.
An external validation of a 14-miRNA model for ovarian cancer, showed a median area under the ROC curve (AUC) of 0.77 in the JanusRNA test sets when evaluating cases with blood samples collected close (<2 years) to diagnosis, as compared to those diagnosed more distant (2-7 years) from diagnosis.
We utilized machine learning models to evaluate circulating RNA and found that smokers diagnosed with lung cancer up to 10 years later, can be robustly differentiated from healthy controls with an average AUC of 0.76 (95% CI, 0.68-0.83). The strongest models, taking time to diagnosis and histology into account, had high discrimination for non-small cell LC diagnosed between 6 and 8 years after blood collection, with an AUC of 0.82 (95% CI, 0.76-0.88), and small-cell LC with samples between 2 and 5 years after blood collection, with an AUC of 0.89 (95% CI, 0.77-1.0), before diagnosis. Models on testicular cancer showed the strongest differential expressed signals 7 years before diagnosis.
In the cancer-free control group, the serum RNA repertoire included 258 miRNAs, 441 piwi-interacting RNAs, 411 transfer RNAs, 24 small nucleolar RNAs, 125 small nuclear RNAs and 123 miscellaneous RNAs. Investigating associations between circulating RNAs and common traits such as age, sex, smoking and BMI showed that RNA levels are highly impacted by age and smoking.
Conclusion/implications for practice or policy
We demonstrate that serum RNAs can be promising pre-diagnostic biomarkers for several cancer types, from early detection to risk assessment. The differentially expressed RNAs were typically associated with cancer related pathways.