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

Abstract

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.

Keywords: biomarker; bone metastasis; pancreatic neuroendocrine neoplasms.

Figure 1

Serum CY18 and CA125 levels in patients with pancreatic neuroendocrine neoplasm (PanNEN): (a) Comparison of serum CY18 between PanNEN patients with bone metastasis (BMets) versus PanNEN without BMets (p = 0.04); (b) Comparison of serum CA125 between PanNEN with BMets versus PanNEN without BMets (p = 0.01). Abbreviations: CY18, cytokeratin 18; CA125, cancer antigen 125.

Figure 2

Performance of serum CA125 and CY18 for detecting PanNEN patients with bone metastases (BM-PanNET patients). The receiver operating characteristic (ROC) curves and the area under the curves (AUC) for BM-PanNEN patients versus non-BM-PanNEN patients are displayed: (a) Individual ROC curve and AUC for serum CA125 (AUC 0.77, 95% CI 0.59–0.95. p < 0.01); (b) Individual ROC curve and AUC for serum CY18 (AUC 0.72, 95% CI 0.53–0.91. p = 0.03); (c) ROC curve and AUC for serum CA125 and CY18 combination (AUC 0.78, 95% CI 0.59–0.95. p < 0.01).