Profiles of FGF2, HGF, Fas/CD95, CASP9, ALDH1A1, and GLUT1 in GEP-NETs: A Comparative Tumor–Margin Study Based on Protein Concentration

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are characterized by substantial biological heterogeneity and complex regulation of apoptosis, metabolism, and angiogenesis. The aim of this study was to evaluate the concentrations of selected proteins: FGF2, HGF, Fas/CD95, CASP9, ALDH1A1, and GLUT1 in tumor and margin samples and assess correlations with clinical and demographic parameters. A total of 59 samples from patients with GEP-NETs were analyzed using multiplex immunoassay and ELISA methods. Significant differences in protein expression between tumor and margin tissues were observed. Fas/CD95 levels were lower in tumor samples, whereas HGF concentration was higher. Elevated HGF, FGF2 and Fas/CD95 levels were associated with advanced tumor stage. HGF and GLUT1 concentrations varied depending on nodal status, while FGF2, Fas/CD95, and CASP9 levels were increased in metastatic cases. Additionally, differences related to tumor localization and the influence of smoking and alcohol consumption were identified. Dysregulation of apoptotic, metabolic, and angiogenic pathways plays a crucial role in GEP-NETs progression and highlights the importance of the tumor microenvironment. GEP-NET exhibit biological heterogeneity and complex progression driven by multiple interacting molecular pathways. The factors analyzed may have potential significance as biomarkers of disease progression; however, their exact role requires further investigation in larger, prospective cohorts.