ENETS studies

Project title: "Role of Chromogranin A-derived fragments as pancreatic neuroendocrine tumor (PanNET) biomarkers and their involvement in PanNET biology."

• AIM 1: to evaluate Chromogranin A (CgA)-derived fragments as PanNET biomarkers.
• Vasostatin-1 (VS-1), the N-terminal fragment of CgA, is a promising PanNET biomarker, as its plasma levels correlate with the presence of pathological features of aggressiveness and significantly decrease after surgical resection, differently from those of CgA and other CgA-derived fragments (pancreastatin and vasostatin-2). Higher VS-1 plasma levels are also associated with disease relapse.

• AIM 2: to characterize the proteolytic fragmentation of CgA in PanNETs through the investigation of CgA cleavage in circulation, in PanNET tissue and in in vitro models.
• Pancreatic neuroendocrine neoplasms (PanNENs) cell lines BON-1 and NT-3 as well as patient-derived islet-like tumoroids retain CgA cleavage, producing and secreting a considerable amount of total-CgA, full-length CgA and VS-1. CgA fragmentation seems to occur within the neuroendocrine cells as CgA-derived fragments can be measured also in the cell lysate and not only in the supernatant.

Principal investigator: San Raffaele Scientific Institute, Experimental Oncology Division - Pancreatic Surgery Unit, Valentina Andreasi

This project is supported through an ENETS Translational Medicine Fellowship.