TY - JOUR
T1 - Vasostatin-1
T2 - A novel circulating biomarker for ileal and pancreatic neuroendocrine neoplasms
AU - Corsello, Andrea
AU - Filippo, Luigi Di
AU - Massironi, Sara
AU - Sileo, Federica
AU - Capuzzo, Anna Dolcetta
AU - Gemma, Marco
AU - Carlucci, Claudia
AU - Cusini, Claudio
AU - Colombo, Barbara
AU - Dallatomasina, Alice
AU - Franchi, Giulia Maria
AU - Corti, Angelo
AU - Manzoni, Marco Federico
PY - 2018/5/1
Y1 - 2018/5/1
N2 - Background Chromogranin A (CgA) is a plasma biomarker widely used in the follow-up of patients with neuroendocrine neoplasms (NENs). However, its accuracy as a tumor biomarker is relatively low because plasma CgA can increase also in patients with other diseases or in subjects treated with proton-pump inhibitors (PPIs), a class of widely-used drugs. Methods In the attempt to identify a more reliable biomarker for NENs, we investigated, by ELISA, the circulating levels of full-length CgA (CgA1-439) and of various CgA-derived fragments in 17 patients with ileal or pancreatic NENs, 10 healthy controls, and 21 healthy volunteers before and after treatment with PPIs. Results Patients with ileal or pancreatic NENs showed increased plasma levels of total-CgA and CgA1-76 fragment (vasostatin-1, VS-1) compared to controls [median (25th-75th-percentiles); total-CgA: 1.85 nM (1.01–4.28) vs 0.75 nM (0.52–0.89), p = 0.004; VS-1: 2.76 nM (1.09–7.10) vs 0.29 nM (0.26–0.32), p<0.001, respectively], but not of CgA1-439 or CgA1-373 fragment. VS-1 positively correlated with total-CgA (r = 0.65, p<0.001). The Receiver Operating Characteristic area under the curve was 0.9935 for VS-1 and 0.8824 for total-CgA (p = 0.067). Treatment of patients with somatostatin analogues decreased both total-CgA and VS-1. In contrast, administration of PPIs increased the plasma levels of total-CgA, but not of VS-1. Conclusion These findings suggest that plasma VS-1 is a novel biomarker for ileal and pancreatic NENs. Considering that VS-1 is a well-defined fragment not induced by proton-pump inhibitors, this polypeptide might represent a biomarker for NENs diagnosis and follow-up more accurate and easier to standardize than CgA.
AB - Background Chromogranin A (CgA) is a plasma biomarker widely used in the follow-up of patients with neuroendocrine neoplasms (NENs). However, its accuracy as a tumor biomarker is relatively low because plasma CgA can increase also in patients with other diseases or in subjects treated with proton-pump inhibitors (PPIs), a class of widely-used drugs. Methods In the attempt to identify a more reliable biomarker for NENs, we investigated, by ELISA, the circulating levels of full-length CgA (CgA1-439) and of various CgA-derived fragments in 17 patients with ileal or pancreatic NENs, 10 healthy controls, and 21 healthy volunteers before and after treatment with PPIs. Results Patients with ileal or pancreatic NENs showed increased plasma levels of total-CgA and CgA1-76 fragment (vasostatin-1, VS-1) compared to controls [median (25th-75th-percentiles); total-CgA: 1.85 nM (1.01–4.28) vs 0.75 nM (0.52–0.89), p = 0.004; VS-1: 2.76 nM (1.09–7.10) vs 0.29 nM (0.26–0.32), p<0.001, respectively], but not of CgA1-439 or CgA1-373 fragment. VS-1 positively correlated with total-CgA (r = 0.65, p<0.001). The Receiver Operating Characteristic area under the curve was 0.9935 for VS-1 and 0.8824 for total-CgA (p = 0.067). Treatment of patients with somatostatin analogues decreased both total-CgA and VS-1. In contrast, administration of PPIs increased the plasma levels of total-CgA, but not of VS-1. Conclusion These findings suggest that plasma VS-1 is a novel biomarker for ileal and pancreatic NENs. Considering that VS-1 is a well-defined fragment not induced by proton-pump inhibitors, this polypeptide might represent a biomarker for NENs diagnosis and follow-up more accurate and easier to standardize than CgA.
UR - http://www.scopus.com/inward/record.url?scp=85046673934&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046673934&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0196858
DO - 10.1371/journal.pone.0196858
M3 - Article
AN - SCOPUS:85046673934
VL - 13
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 5
M1 - e0196858
ER -