Role of Selected Circulating Tumor Biomarkers in Patients with Skeletal Metastatic Pancreatic Neuroendocrine Neoplasms

We investigated the diagnostic capacity of selected circulating biomarkers (CBMs) for the early detection of bone metastasis (BMets) in patients with pancreatic neuroendocrine neoplasms (PanNENs). A total of 115 patients with PanNENs and 40 controls were enrolled. We measured the serum levels of ferritin, cytokeratin 18 (CY18), CA19-9, CA125, AFP, CEA, and beta-2 microglobulin (B2M). A total of eight PanNEN patients developed BMets, and one hundred seven remained BMets-free. We observed a significantly higher level of CA125 and CY18 in BMets patients vs. non-BMets patients (p = 0.01 and p = 0.04, respectively). CA125, CY18, and B2M area under receiver operator characteristic (AUROC) analyses differentiated both patients groups; CA125 area under the curve (AUC) 0.77, p < 0.01; CY18 AUC data were 0.72, p = 0.03, and B2M AUC 0.67, p = 0.02. On the basis of CBM metrics in both subgroups, we reached a sensitivity/specificity for CA125 of 75/76%; for CY18 of 75/69%, for B2M of 100/50%, for CA125, and the CY18 combination of 93/90%, respectively. According to current results, CA125 and CY18 seem to have the potential capacity as fair biomarkers for BMets detection, despite the small number of cases. Further studies are warranted in the larger PanNEN patient group.