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Cancer Lett. 2019 Jun 28;452:237-243. doi: 10.1016/j.canlet.2019.03.009. Epub 2019 Mar 21.

Vimentin-positive circulating tumor cells as a biomarker for diagnosis and treatment monitoring in patients with pancreatic cancer.

Author information

1
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China.
2
Department of Hepatobiliary Pancreatic Surgery, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China.
3
Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
4
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
5
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China. Electronic address: liangtingbo@zju.edu.cn.
6
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, Hangzhou, China; Innovation Center for the Study of Pancreatic Diseases, Zhejiang Province, China. Electronic address: shirleybai@zju.edu.cn.

Abstract

The identification of circulating tumor cells (CTCs) relies on epithelial tumor cell markers. In the present study, we aimed to determine whether cell-surface vimentin could be a biomarker to isolate CTCs in pancreatic ductal adenocarcinoma (PDAC). Vimentin was identified as highly expressed on the surface of mesenchymal-phenotype pancreatic tumor cells. Vimentin+ CTCs were detected in 76% of patients with PDAC (76/100) using CTCs enriched via a microfluidic assay. A cut-off value of two vimentin+ CTCs distinguished patients with PDAC from healthy individuals. Combined vimentin+ CTCs and Carbohydrate antigen 19-9 provided favorable diagnostic potency, with an area under the curve of 0.968. Vimentin+ CTCs counts correlated with the change in tumor burden for patients undergoing resection. Significantly reduced CTC counts were observed after chemotherapy in subjects that responded to treatment. Preoperatively higher CTCs counts correlated with shortened recurrence-free survival. Taken together, vimentin+ CTCs could be a reliable biomarker in pancreatic cancer. The enrichment of mesenchymal CTCs complements the strategy of capturing epithelial CTCs, allowing a more thorough interrogation of the biology and clinical significance of CTCs in PDAC.

KEYWORDS:

Biomarker; CTCs; Epithelial-mesenchymal transition; Pancreatic ductal adenocarcinoma

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