Endoscopic Ultrasound-Guided Acquisition of Portal Venous Circulating Tumor Cells as a Potential Diagnostic and Prognostic Tool for Pancreatic Cancer

Abstract

Background: Circulating tumor cells (CTCs) were a promising liquid biopsy for pancreatic cancer (PC) but circulate in low counts in peripheral blood. We evaluated the diagnostic and prognostic values of portal vein (PoV) CTCs in PC patients. Methods: PoV was aspirated under EUS guidance from 40 patients with suspected pancreaticobiliary cancers. Epithelial-mesenchymal-transition-related subtypes of CTCs were identified via immunofluorescence using EpCAM and Twist antibodies. The diagnostic and prognostic performance of PoV CTCs was investigated by receiver-operating characteristic (AUC) curve and Kaplan-Meier survival analysis. Results: In total, 40 patients including 31 with PC, 4 with non-pancreatic periampullary cancer and 5 with benign pancreatic diseases (BPD) were enrolled. CTCs were detected more in PoV compared with peripheral blood. PoV CTC numbers in BPD patients were lower than in PC patients. The number of PoV CTCs, especially mesenchymal-CTCs (M-CTCs), was positively correlated with the tumor burden, instead of epithelial-CTCs (E-CTCs). The combination of PoV CTC numbers and CA19-9 demonstrated better diagnostic efficiency (AUC value 0.987) than either alone in differentiating PC with BPD. Moreover, the diagnostic efficacy of PoV CTCs and M-CTCs were obviously better than that of E-CTCs and CA19-9 in distinguishing early and late stage PC. Lastly, high PoV CTC and M-CTC numbers were both associated with shorter overall survival. Conclusion: Acquisition of the PoV samples in PC patients via EUS-guided procedures has been proved safe and feasible. PoV CTCs, especially M-CTCs, have great potentials in diagnosing and predicting the prognosis of PC, especially in combination with CA19-9.

Prognostic Implications of Portal Venous Circulating Tumor Cells in Resectable Pancreatic Cancer

“…Based on this finding, some studies compared portal and peripheral CTCs in patients with pancreatic cancer. Two recent studies of patients with advanced or metastatic pancreatic cancer showed a higher CTC detection rate in the portal vein than in the peripheral vein, and the number of CTCs derived from the portal vein, rather than CTCs from the peripheral vein, was associated with OS [ 11 , 12 ]. However, studies that included only patients with resectable pancreatic cancer showed inconsistent results.…”

“…The portal CTC detection rate was greater than 80% in some studies, including our study, in which portal CTC was significantly correlated with survival. However, the portal CTC detection rate remained in the 60% range in studies that did not show such correlation [ 11 , 12 , 13 , 14 ].…”

“…To our knowledge, this is the first study to demonstrate the association between the number of portal CTCs and regional lymph node metastasis in patients with resectable pancreatic cancer. Zhang et al also reported that the number of portal CTCs was related to lymph node metastasis, but the study included patients with metastatic or locally advanced diseases, in addition to resectable pancreatic cancer [ 12 ]. Lymph node metastasis is particularly important in resectable pancreatic cancer because it is associated with early recurrence and poor clinical outcome [ 21 ].…”

“…The small number of subjects in this study might have obscured the differences in prognosis according to CTC phenotype. Zhang et al’s study using Twist as a mesenchymal CTC marker reported a greater number of Twist + CTCs compared with EpCAM + CTCs in the portal vein [ 12 ]. Therefore, the absence of additional mesenchymal markers, such as Twist, in addition to vimentin in this study might explain the absence of a difference in prognosis according to CTC phenotype.…”

Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Review of Their Genetic Characteristics and Mouse Models

“…Targeted genotyping ( GNAS / KRAS ) of cell-free DNA (cfDNA) from blood samples can also distinguish IPMN from control cases (sensitivity, 81%; specificity, 84.2%) and the amount of cfDNA detected is much higher in metastatic pancreatic ductal adenocarcinoma (PDAC) than in IPMN for differential diagnosis [ 51 ]. Considering the higher abundance of circulating tumor cells (CTCs) in portal vein blood compared to in peripheral blood, researchers have discovered that the count of mesenchymal-CTCs and vimentin+ CTCs correlates with a poorer differentiated tumor and a shorter survival [ 52 , 53 ].…”