Abstract
Circulating tumor cells (CTCs) are useful biomarkers of many solid tumors, but are infrequently detected in early stage pancreatic ductal adenocarcinomas (PDACs). The first drainage of pancreatic venous blood flow come to portal vein and pass through the liver, and they finally go out for peripheral blood. We thought that comparing CTCs from portal vein and peripheral blood could enable us to understand the clinical meaning of CTCs from each different site in PDACs. Therefore, we aimed to determine 1) whether CTCs could be reliably identified in early stages (operable) of PDACs, 2) if there are any differences in the detected number of CTC in portal vein blood and peripheral blood, and 3) whether CTCs can be sensitive biomarkers for the prognosis of resectable PDAC patients. Newly diagnosed PDAC patients who underwent operation with curative intention between 2013 and 2015 were prospectively enrolled. Blood draws from portal and peripheral vein ran through the microfabricated porous filter, and anti-epithelial cell adhesion molecule (EpCAM) and anti-Plectin-1 antibodies were used for CTC identification. Baseline clinical characteristics, tumor characteristics, treatment, and clinical outcomes were assessed. The clinical stages of the 32 enrolled patients were as follows: IA/IB 1 (3.1%); IIA 9 (28.1%); IIB 17 (53.1%); III 5 (15.6%). Twenty-seven patients (84.4%) received R0 resection, while five patients (15.6%) received R1 resection. EpCAM+ CTCs were detected in 20 portal blood (62.5%) and 22 peripheral blood (68.8%). Plectin-1+ CTCs were identified in 14 portal blood (43.8%) and 16 peripheral blood (50%). Plectin-1-expressing CTCs were picked from CTC platform (microfabricated porous filter) and we could find out all KRAS mutation. Patients with detectable EpCAM+ CTC less than one in peripheral blood showed longer overall survival (OS) compared to patients with detectable CTCs more than one (35.5 months vs. 16.0 months). EpCAM and Plectin-1 successfully identified CTCs at the early stage of PDACs. Also, the number of CTCs could be a prognostic marker for survival in resectable PDACs.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis due to early metastatic spread
To evaluate the feasibility of EpCAM and Plectin-1 antibodies in verifying circulating tumor cell (CTC) of PDAC patients, the expressions of EpCAM and Plectin-1 were examined in human PDAC cell lines by flow cytometry
white blood cells (WBCs) that could be contaminated during CTC preparation rarely expressed EpCAM or Plectin-1 on their surfaces (
Summary
Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis due to early metastatic spread. 20% of patients have resectable PDAC at diagnosis, and only 20% of them survive for more than 5 years [2]. Early diagnosis and curative resection is the only means to improve prognosis of PDAC patients. There are no useful biomarkers for early diagnosis, and predicting prognosis and treatment response. Among several novel biomarker candidates, circulating tumor cell (CTC) is one of the most promising candidates. It is easy to detect CTCs in the peripheral circulation of cancer patients where tumor drainages are into the peripheral circulation. The first venous drainage of PDAC is into the portal circulation, leading some difficulties to capture CTCs in peripheral circulation. The investigation of CTCs in portal vs peripheral blood may give us insights into the importance of tumor drainage pattern in CTC detection
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