Circulating microRNAs as dynamic biomarkers of response to treatment with FOLFIRINOX in advanced pancreatic ductal adenocarcinoma

Abstract

Background: With novel treatments arising rapidly, biomarkers for personalized medicine are essential. Only one third of the patients with advanced pancreatic ductal adenocarcinoma (PDAC) show clinical benefit from FOLFIRINOX chemotherapy. Circulating microRNAs (miRNAs) have been proposed as minimally-invasive biomarkers. Our aim was to identify blood-based miRNAs as predictive and monitoring biomarkers. Methods: Patients with advanced PDAC receiving FOLFIRINOX therapy (n=54) were prospectively enrolled. MiRNAs were isolated from plasma collected at several time points. In a first “discovery cohort”, differentially expressed miRNAs were identified using a microarray panel. Emerging miRNAs were evaluated by RT-PCR in a “validation cohort” in extracellular vesicles of 16 non-progressive patients. Results: MiR-29a emerged as a potential biomarker in both analyses. In particular, it was significantly upregulated (2·36-fold change, p<0·0024) in extracellular vesicles after five cycles of FOLFIRINOX in non-progressive disease. Interestingly, the expression of circulating free miR-29a was significantly lower than miR-29a expression in extracellular vesicles than (p<0·0001). Conclusion: Altered levels of miR-29a in plasma and extracellular vesicles can anticipate progression of PDAC and guide more effective therapeutic strategies. These findings open new opportunities to explore blood-based miRNA profiles and specific miRNA candidates to select patients most likely to respond to FOLFIRINOX.