CIRCUS
Research type
Research Study
Full title
CIRcular and Non-coding RNAs as Clinically USeful Biomarkers in Pancreaticobiliary Cancers (CIRCUS)
IRAS ID
277406
Contact name
Adam Frampton
Contact email
Sponsor organisation
Royal Surrey NHS Foundation Trust
Duration of Study in the UK
3 years, 6 months, 0 days
Research summary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. In the UK, incidence is almost equal to mortality-rate. Unfortunately, symptoms are non-specific and most patients present late with advanced disease, with poor survival-outcomes. Whilst large sequencing experiments have described the genetic make-up associated with PDAC and its variability, the role of certain molecules called ‘non-coding RNAs’ in the development of cancer is unclear. One recently recognised member of this family is circular RNA (circRNA), these natural “circles” of RNA have been shown to regulate cancer-related genes, and act as cancer ‘biomarkers’. They have proven to be abundant and stable in tumour tissue and peripheral blood.
Firstly, we will first perform an in-depth evaluation of circRNA expression “signatures” in fresh tissue biopsies of PDAC utilising microarray. Samples will be taken from patients who undergo surgery to remove the pancreas, these will be taken after removal when surplus to clinical requirement. This will allow identification of potentially important circRNA biomarkers for further evaluation.
We will validate candidate circRNAs expression in further fresh tissue samples and evaluate the circRNAs ‘signature’ as a diagnostic biomarker in peripheral blood as a clinical useful sample site. During the patient’s clinical pathway there may be the opportunity to collect other biomaterials that are taken as part of standard treatment and surplus to clinical requirements, these include bile and biopsy samples. We will evaluate the expression of candidate circRNAs in these biomaterials. In addition to evaluating circRNAs ability to act as a diagnositic biomarker we will assess their ability to prognosticate outcomes and both predict and monitor response to surgery and chemotherapy, potentially allowing ‘tailor-made’ treatment strategies.
Finally, we will investigate their potential molecular interactions and mechanisms using 'in silico' analyses and by evaluating their association with the features of malignancy in immortal PDAC cell lines.
REC name
South West - Central Bristol Research Ethics Committee
REC reference
20/SW/0105
Date of REC Opinion
3 Aug 2020
REC opinion
Further Information Favourable Opinion