Relationship between heavy metals and miRNAs in pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, characterized by poor prognosis due to the late diagnosis and chemotherapy resistance. Both genetic and environmental factors, including heavy metals exposure are involved in PDAC development. In this study, we evaluated the association between a panel of miRNAs and metals with PDAC, and subsequently assessed their correlation using Spearman’s test to investigate potential biological links. miRNA expression was analysed in the serum of PDAC patients (n = 37) compared to healthy controls (n = 20), as well as in tumour biopsies (n = 23) versus adjacent healthy tissue (n = 21). For metals, whole blood and tumour biopsies were examined and compared with their respective healthy counterparts. The metals considered were cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), manganese (Mn), lead (Pb), nickel (Ni), iron (Fe), zinc (Zn), and selenium (Se); the analysed miRNAs included miR-361–3p, miR-320d, miR-20b–5p, miR-4486, miR-216a–5p, miR-216b–5p, miR-324–5p, miR-125a–5p. Our results showed that miR-320d, miR-20b–5p, miR-4486, miR-216a–5p and miR-216b–5p were significantly overexpressed in PDAC serum samples compared to controls as well as PDAC patients showed high concentration of Cr and Cu. On the other hand, no significant differences were reported between PDAC biopsies and healthy counterpart. However, higher concentration of Cu, Fe, Se, and Zn were observed in tumour samples. Spearman's Rank Correlation analysis revealed a positive correlation between miR-216a-5p and Mn, Cd and Zn and negative correlation with miR-320d and miR-361–3p in tissue samples. While in serum, miR-361–3p was positively correlated with Cu, suggesting a potential link between oxidative stress regulation and PDAC development. This study suggests that specific miRNAs correlate with metals in PDAC, such as miR-361–3p with Cu and miR-216a-5p with Mn, hinting at a potential role of metal homeostasis in tumour-related pathways. However, these findings warrant further validation and functional studies, and may provide novel insights for biomarker development and therapeutic strategies in PDAC.