Vasostatin-1: A novel circulating biomarker for ileal and pancreatic neuroendocrine neoplasms

Abstract

BackgroundChromogranin 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.MethodsIn 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.ResultsPatients 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.ConclusionThese 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.

A Preoperative Clinical Risk Score Including C-Reactive Protein Predicts Histological Tumor Characteristics and Patient Survival after Surgery for Sporadic Non-Functional Pancreatic Neuroendocrine Neoplasms: An International Multicenter Cohort Study

“…Despite a 95% negative predictive value for recurrence in patients with zero points, the scoring system is limited by the restricted availability of CgA in some centers and possible falsely elevated CgA levels [23]. To overcome parts of these limitations, vasostatin-1 (VS-1), a cleavage fragment of CgA, has recently been explored as a prognostic biomarker, but VS-1 assessment is also not generally available and prospective validation is pending [24,25].…”

Pancreatic neuroendocrine tumors: Therapeutic challenges and research limitations

“…NSE is also a non-specific biomarker because increase level of this molecule is associated with brain injury[ 86 ]. Nevertheless, vasostatin-1 (VS-1): The N-terminal fragment of chromogranin A (CgA), has recently been identified to be more accurate than CgA as neuroendocrine biomarker and the plasma levels of VS-1 are not altered by proton pump inhibitors (PPI) used in gastrinoma[ 87 ].…”

Establishment and Investigation of a Multiple Gene Expression Signature to Predict Long‐Term Survival in Pancreatic Cancer

“…It is involved in pancreatic beta cell secretion, negative regulation of insulin, and hormone secretion ( Figure 1(b) ). In recent years, some previous works have revealed CHGA as a novel biomarker for PC [ 30 – 32 ]. ITGB6 and LAMC2 had been reported to be associated with activation of the EMT, cell adhesion, TGF β , PI3K-AKT, and MAPK pathways [ 33 – 39 ], which are all involved in PC tumorigenesis.…”