The Role of Circular RNAs in Pancreatic Ductal Adenocarcinoma and Biliary-Tract Cancers

SIMPLE SUMMARY: Pancreatic and biliary tract cancers often present with non-specific symptoms, resulting in diagnosis at a late stage. This may be too late for curative surgery. Earlier detection and characterisation may guide treatment options and increase survival. Natural “circles” of RNA (circRNAs) are shown to regulate cancer-related genes, and act as cancer “biomarkers”. Recent research has shown that circRNAs are both abundant and stable, both of which are desirable characteristics for clinically useful biomarkers. In this systematic review, we describe the roles of circRNAs in pancreatic and biliary tract cancers, summarise the current published research and explore their utility as a biomarker. A total of 32 articles were included: 22 considering Pancreatic Cancer, 7 for Bile Duct Cancer and 3 for Gallbladder Cancer. CircRNA proved an exciting prospect as a biomarker for these cancers and future work should continue to develop and expand this field of research. ABSTRACT: Pancreatic Ductal Adenocarcinoma (PDAC) and biliary-tract cancers (BTC) often present at a late stage, and consequently patients have poor survival-outcomes. Circular RNAs (circRNAs) are non-coding RNA molecules whose role in tumourigenesis has recently been realised. They are stable, conserved and abundant, with tissue-specific expression profiles. Therefore, significant interest has arisen in their use as potential biomarkers for PDAC and BTC. High-throughput methods and more advanced bioinformatic techniques have enabled better profiling and progressed our understanding of how circRNAs may function in the competing endogenous RNA (ceRNA) network to influence the transcriptome in these cancers. Therefore, the aim of this systematic review was to describe the roles of circRNAs in PDAC and BTC, their potential as biomarkers, and their function in the wider ceRNA network in regulating microRNAs and the transcriptome. Medline, Embase, Scopus and PubMed were systematically reviewed to identify all the studies addressing circRNAs in PDAC and BTC. A total of 32 articles were included: 22 considering PDAC, 7 for Cholangiocarcinoma (CCA) and 3 for Gallbladder Cancer (GBC). There were no studies investigating Ampullary Cancer. Dysregulated circRNA expression was associated with features of malignancy in vitro, in vivo, and ex vivo. Overall, there have been very few PDAC and BTC tissues profiled for circRNA signatures. Therefore, whilst the current studies have demonstrated some of their functions in these cancers, further work is required to elucidate their potential role as cancer biomarkers in tissue, biofluids and biopsies.