# Serum Visfatin/eNAMPT as a Biomarker in Pancreatic and Small Intestine Neuroendocrine Tumors: A Cross-Sectional Study and Future Perspectives

## TL;DR

This study shows that measuring serum visfatin could help diagnose pancreatic and small intestine neuroendocrine tumors, offering a potential new biomarker.

## Contribution

The first study to explore serum visfatin as a diagnostic biomarker for neuroendocrine tumors.

## Key findings

- Serum visfatin levels were significantly higher in NET patients compared to controls.
- Visfatin showed moderate diagnostic performance with 75.3% sensitivity and 58.6% specificity.
- Visfatin levels were not influenced by tumor grade, site, or patient characteristics.

## Abstract

This study demonstrates for the first time the potential utility of serum visfatin/eNAMPT measurements as a diagnostic biomarker for neuroendocrine tumors (NETs). Visfatin/eNAMPT concentrations are increased in patients with metastatic pancreatic and small intestinal NETs and show potential in distinguishing NETs from controls, regardless of tumor and patient characteristics. As a biomarker, visfatin could act as a bridge between currently used imperfect monoanalytes such as chromogranin A and expensive multianalytes such as NETest. Although serum visfatin levels might not directly reflect tissue NAMPT expression, we also review visfatin’s role in a therapeutic setting in the context of NAMPT inhibitors, researched in previous studies.

Background: Neuroendocrine tumors (NETs) remain a problematic area in endocrine oncology due to their non-specific symptoms and lack of reliable biomarkers. Visfatin/eNAMPT’s involvement in tumorigenesis has been described in several malignancies. In NETs, NAMPT inhibition was explored as a potential therapeutic option; however, serum visfatin and its role as a biomarker have not been studied. Objectives: We aimed to measure serum visfatin concentrations in NETs and evaluate visfatin’s potential as a diagnostic biomarker. Methods: We conducted a single-center, cross-sectional study of 77 patients with NETs (33 pancreatic and 44 small intestinal) and 29 controls. Patient demographics, tumor characteristics, and clinical data were analyzed, and serum visfatin levels were measured using ELISA. Statistical analyses were performed in Python, including Mann–Whitney U and Kruskal–Wallis tests, Spearman’s correlation, multiple linear regression, and ROC curve analysis. Results: Serum visfatin was higher in NETs compared to controls (median [IQR]: 6.94 [2.11–236.17] vs. 1.59 [1.1–9.24] ng/mL, p = 0.004). ROC curves showed moderate diagnostic performance (AUC = 0.68), with concentrations above 2.11 ng/mL achieving 75.3% sensitivity and 58.6% specificity. In NETs, visfatin did not differ based on WHO grade (G1/G2, p = 0.31), primary site (pancreas/small intestine, p = 0.95), sex (p = 0.89), age (p = 0.13), and when stratified by primary site and grade (p = 0.18). Multiple linear regression confirmed no association between visfatin and the study variables (R-squared = 0.036, all p > 0.2). Conclusions: This is the first study examining serum visfatin as a diagnostic biomarker in NETs. Visfatin concentrations show moderate discriminatory ability between NETs and controls, independent of tumor and clinical characteristics. Further research should involve larger cohorts and comparisons to established biomarkers.