Clinical Significance of Circulating Tumor Cells in Unresectable Pancreatic Ductal Adenocarcinomas

Abstract

Background: Circulating tumour cells (CTCs) have emerged as liquid biopsy biomarker providing non-invasive assessment of cancer progression and biology. We investigated whether longitudinal analysis of CTCs could monitor disease progression, response to chemotherapy, and survival in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). Methods: CTCs were isolated using a centrifugal microfluidic disc from serially collected peripheral blood with clinical assessments. CTCs were enumerated with immunostaining against Epithelial cell adhesion molecule, Cytokeratin, Plectin-1 and CD45. Results: CTCs were detected in 92.3% of 52 patients with unresectable PDAC at the time of diagnosis. CTC numbers were not statistically different across tumour sizes, stages and metastatic sites. The absolute CTC counts after chemotherapy was inversely related to survival, and the decreased number of CTCs after the first cycle of chemotherapy was significantly associated with longer survival. Conclusions: Identifying CTCs and monitoring CTC changes after chemotherapy could be a useful prognostic marker for survivals in patients with unresectable PDACs. Funding: This work was supported by a grant from SK Chemical Research Fund of the Korean Society of Gastroenterology (Grant No.800 20130378) and a grant from Korean Gastroenterology Fund for Future Development. This study was granted by the Korean Health Technology R&D Project, Ministry of Health & Welfare funded by the Korean Government (Grant No. HI12C1845) HI12C1845), and work by Y.K.Cho was partially supported by IBS R020 D1 funded by the Korean Government. This research was supported by Collaborative Genome Program for Fostering New Post Genome industry through the National Research Foundation (NRF) funded by the Korean governnment (MSIT) (Grant No. NRF-2017M3C9A5031002), and also supported by National Research Foundation (NRF) grant funded by the Korean government (MSIT) (Grant No. 2019R1C1C1008646). Clinical Trial Registration ID #: NCT02934984