Introduction: Effective Pancreatic ductal adenocarcinoma (PDAC) biomarkers are urgently needed for early diagnosis and prognosis. Circular RNAs (circRNAs), characterised by their circular structure and regulatory potential, have emerged as promising candidates due to their stability and abundance. This study aimed to explore circRNA expression in PDAC cell lines and human blood for potential biomarker application.

Methods: PDAC cell lines were analysed via microarray to establish circRNA, micro RNA, and messenger RNA expression patterns. A novel bioinformatical pipeline was used to identify potential circRNA candidates. Circularity was confirmed by RNAse R resistance and results validated. Total RNA sequencing of clinical samples, including plasma and exosome components, elucidated circRNA expression patterns in patient biomaterials. A PDAC patient biobank was established, with ongoing recruitment of patients for molecular research.

Results: Significant differences in circRNA expression between PDAC and benign cell lines were observed. Six candidates were highlighted for validation, three of which were associated with the TADA2A cluster. These circRNAs all exhibited resistance to RNAse R. A large volume of circRNAs were expressed in plasma and exosomes, and these were more abundant than linear homologs. However, limited sample size hindered differential expression analysis among patients.

Conclusions: This study introduces a novel pipeline for circRNA research in cells. Despite small sample sizes, circRNAs showed promise as blood-based biomarkers due to their abundance and stability in plasma and exosomes. Further investigation is warranted, with this research providing valuable preliminary data to support future funding and research endeavours.