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Prognostic implication of portal venous circulating tumor cells in resectable pancreatic cancer
Background
Circulating tumor cells (CTCs) may be promising prognostic biomarkers in patients with advanced cancer. However, the paucity of CTCs in peripheral blood is the major challenge of clinical implication especially in early-stage cancer. Our study aimed to investigate whether the portal venous CTC can be a biomarker for early recurrence and poor prognosis in pancreatic cancer.
Methods
Patients who were scheduled to undergo upfront curative resection for pancreatic cancer from September, 2017 to June, 2019 at a single tertiary hospital were consecutively enrolled in this prospective study. Intraoperatively, 7.5 mL blood was collected from the portal vein by direct puncture with a syringe and 7.5 mL peripheral venous blood was also collected. The detection and identification of circulating tumor cell (CTC) were performed using immunofloresence staining and examined under fluorescene microscope. We used 4-color staining protocol for CTC identification; DAPI (blue) for nucleated cells, CD45 (red) as a leukocyte marker, EpCAM or CK (yellow) as an epithelial marker, and vimentin (green) as a mesenchymal cell marker.
Results
During study period, peripheral blood CTC sampling was performed in 33 patients, of which portal vein CTC sampling was performed in 28. The median portal venous CTCs (2.5, interquartile ranges [IQR] 1-7.75) were significantly higher than the median peripheral venous CTCs (1, IQR 0-2, p < 0.001). Higher stage and regional lymph node metastasis were related with higher number of CTCs (≥3) in portal venous blood. Patient with low portal venous CTCs (≤ 2) showed better overall (not reached vs. 16.5 months, p=0.002) and recurrence free (13.4 vs. 7.0 months, p=0.007) survival than those with high portal venous CTCs (≥3). The number of peripheral venous CTCs were not related to overall and recurrence free survival after resection of pancreatic cancer. The phenotype (epithelial vs. mesenchymal) of CTC was not associated with cancer characteristics or prognosis.
Conclusions
Portal venous CTCs can be used as a biomarker to determine prognosis after resection of pancreas cancer. In addition, the Portal CTC acquisition prior to surgery may be useful in determining neoadjuvant chemotherapy in patients with radiologically resectable pancreatic cancer.
Legal entity responsible for the study
The author.
Funding
This work was supported by the Catholic University of Korea, Eunpyeong St. Mary's Hospital Research Institute of Medical Science (2019), the Catholic Medical Center Research Foundation made in the program year of 2020, and a grant from the National Research Foundation of Korea funded by the Korean Government (NRF-2021 R1F1A1062255).
Disclosures
All authors have declared no conflicts of interest.
