The presence of prion protein in surgically resected pancreatic adenocarcinoma: a potentially new biomarker

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers, with a specifically high neurotropism. Among the several new targets for the comprehension of its biology, Prion proteins (PrP) deserve particular mention, since they have a marked neurotropism, but could have also a role in tumorigenesis, as recently demonstrated. However, few in vitro studies in cell cultures showed the occurrence of PrP in PDAC cells. The aim of this study is to evaluate the presence of PrP in vivo in PDAC tissues as a potential new biomarker. Methods: Samples from tumors of 16 patients undergone pancreatic resections from July 2018 to May 2019 at our institution were collected. Immunohistochemistry and western blotting of PDAC tissues were compared with control tissues. Immunohistochemistry was used also to evaluate the localization of PrP and of CD155, a tumoral stem-cell marker. Results: All patients were affected by moderately differentiated PDAC, with perineural invasion in 12/16 cases (75%). According to the western-blot analysis, PrP was markedly expressed in PDAC tissues (438,61 ± 55,41 OD) respect to controls (100 ± 16,97 OD, p<0,001). Immunohistochemistry confirmed these findings, with a higher linear staining of PrP in PDAC ducts (125±12.51 µm vs 79,5±6,4 µm, p<0.001). Finally, PrP and CD155 exactly overlapped in ductal tumoral cells, highlighting the possible relationship of PrP with cancer stemness. Conclusions: Our work provides evidence for increased levels of PrP in PDAC. This might contribute to neurotropism and provides a potential new biomarker. Work is in progress to decipher clinical implications.