Introduction: Despite advances in diagnostical and therapeutical modalities, pancreatic ductal adenocarcinoma (PDAC) remains among malignancies with worst prognosis. In the future, liquid biopsy utilising tumour derived extracellular vesicles (EV) and specific micro RNAs (miRNA) could become a valuable tool for diagnosing PDAC and monitoring treatment response. Plasma miR-10b, -21 and -30 have already been shown to distinguish between PDAC and other chronic conditions of the pancreas or healthy individuals. EV derive from different cells and are present in all body fluids. Molecular cargo of EV, including proteins and miRNAs, is a direct reflection of the physiological and pathological state of the cell of origin. The aim of our study was to evaluate the association of EV size and plasma levels of miR-10b, -21 and -30c with the presence of PDAC and their role as potential biomarkers of PDAC resection radicality.
Hypotheses: H1: Resection of PDAC alters the size of EV isolated from patients’ plasma. H2: Plasma levels of miR-10b, miR-21 and miR-30c drop/normalise after radical resection of PDAC. H3: Vesicular miR-10b, miR-21 and miR-30c are better markers of PDAC resection radicality than free plasma miR-10b, miR-21 and miR-30c.
Methods: This prospective cohort study included 83 patients with PDAC undergoing surgery with curative intent. Relevant patients’ clinical data was acquired and blood samples for EV isolation and quantification as well as for evaluation of miR-10b, -21 and -30c expression in plasma and EV were drawn at different time points.
Results: 50 patients had a PDAC resection performed while in 33 resection was not indicated/possible. Preoperative EV concentration was significantly different between the two patient groups (p = 0.023). In 72.2% patients with PDAC resection mean size of EV one month after surgery was larger compared to values before surgery (p = 0.014), as was also seen in the subgroups of patients with R0 resection (77.3%; p = 0.010). Patients with resection demonstrated a significant change in expression of vesicular miR-10b-5p and miR-21-5p after surgery, while the difference was not significant for miR-30c-5p. The significant difference between expression of miR-21-5p before surgery and one month afterwards was also seen in patients with R0 resection (p = 0.002). Furthermore, one month after surgery, a significant rise in miR-21-5p expression was seen in patients with R0 resection compared to patients with R1/R2 resection (p = 0.031). Regarding the plasma miRNAs, the only significant difference in expression was noted for miR-10b-5p after resection.
Conclusion: Based on the findings of our study, the first hypothesis (H1) of this doctoral dissertation was confirmed, partially also the third hypothesis (H3), while the second hypothesis (H2) was disproved. Changes in miRNA expression and in size or concentration of plasma EV after PDAC resection could potentially be utilised for more precise evaluation of resection radicality. Consequently, chemoradiation would perhaps be given to those patients who would otherwise not receive it. Thus, overall survival could be improved. Furthermore, liquid biopsy with EV and miRNA could prove useful during follow-up after PDAC resection and for evaluation of response to treatment.
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