Circulating Tumor Cells in Pancreatic Cancer: Current Perspectives

Pancreatic cancer is the fourth leading cause of cancer-related death in the USA and Europe; early symptoms and screenings are lacking, and it is usually diagnosed late with a poor prognosis. Circulating tumor cells (CTCs) have been promising new biomarkers in solid tumors. In the last twenty years (1999–2019), 140 articles have contained the key words “Circulating tumor cells, pancreatic cancer, prognosis and diagnosis.” Articles were evaluated for the use of CTCs as prognostic markers and their correlation to survival in pancreatic ductal adenocarcinoma (PDAC). In the final selected 17 articles, the CTC detection rate varied greatly between different enrichment methodologies and ranged from 11% to 92%; the majority of studies used the antigen-dependent CellSearch© system for CTC detection. Fifteen of the reviewed studies showed a correlation between CTC presence and a worse overall survival. The heterogeneity of CTC-detection methods and the lack of uniform results hinder a comparison of the evaluated studies. However, CTCs can be detected in pancreatic cancer and harbor a hope to serve as an early detection tool. Larger studies are needed to corroborate CTCs as valid biomarkers in pancreatic cancer.

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Clinical significance of circulating tumor cells identified by cell-surface vimentin in pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e14562 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e14562-e14562

Author(s):

Tao Wei ◽

Qi Zhang ◽

Tingbo Liang ◽

Xueli Bai

Keyword(s):

Pancreatic Cancer ◽

Cell Surface ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Clinical Significance ◽

Ductal Adenocarcinoma ◽

Rank Test ◽

Epithelial Tumor ◽

Mesenchymal Phenotype

e14562 Background: Identification of circulating tumor cells (CTCs) largely rely on epithelial tumor cell marker. Here we sought to interrogate whether cell-surface vimentin could be a biomarker for isolating CTCs potentially with mesenchymal phenotype in pancreatic ductal adenocarcinoma (PDAC). Methods: In total, 100 PDAC patients, 16 patients with intraductal papillary mucinous neoplasm (IPMN), and 30 healthy individuals were enrolled between December 2016 and November 2017. Potential CTCs were captured in 4 ml blood samples by vimentin antibody-coated microfluidic chip. CTCs were defined as vimentin+CD45-Hoechst+. Results: In vitro experiment showed that vimentin was highly expressed on the surface of pancreatic tumor cells with mesenchymal phenotype. Overall, vimentin+ CTCs were detected in 76% of patients with PDAC, but only in 2 out 30 healthy donors. Besides, five patients (31.3%) with IPMN had vimentin+ CTCs, and 10 CTCs were identified in one case. Using a cut-off value of two cells/4 ml of blood, 65% PDAC patients were positive for vimentin+ CTCs , while the positivity rates for the patients with IPMN and the healthy controls were 25% and 0%, respectively. Combined vimentin+ CTCs and CA19-9 offered a favorable diagnostic potency with area under curve of 0.968. Vimentin+ CTCs counts correlated with change of tumor burden for patients undergoing resection ( P < 0.01). Significant reduction of CTCs counts was observed after chemotherapy for subjects responding to treatment ( P < 0.05). The paired analysis showed that CTC counts was higher in portal vein blood than peripheral blood for 10 patients with available samples ( P < 0.05). Patients with 2 or more CTCs detected had more advanced disease and poorer differentiated tumor. In addition, preoperative higher CTCs counts correlated with shortened recurrence-free survival (Log-rank test: P = 0.02). Conclusions: Vimentin+ CTCs serves as a reliable biomarker in pancreatic cancer. The enrichment of potential mesenchymal CTCs could complement the strategy capturing epithelial CTCs, and provides a way to more thoroughly interrogate the biology and clinical significance of CTCs in PDAC.

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Detection methods for circulating tumor cells in the blood of patients with pancreatic cancer in a pre-operative setting

Pancreatology ◽

10.1016/j.pan.2019.05.312 ◽

2019 ◽

Vol 19 ◽

pp. S117

Author(s):

Emin Mailian ◽

Maximilian Kordes ◽

Aman Russom ◽

Rainer Heuchel ◽

Lennart Eriksson ◽

...

Keyword(s):

Pancreatic Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Detection Methods

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Chylous Ascites, Unusual Association with Ductal Pancreatic Adenocarcinoma with Plasmacytoid Morphology: A Case Report and Literature Review

The Surgery Journal ◽

10.1055/s-0041-1728651 ◽

2021 ◽

Vol 07 (03) ◽

pp. e158-e162

Author(s):

Catalin Bogdan Satala ◽

Ioan Jung ◽

Tivadar Jr. Bara ◽

Vlad Tudorache ◽

Simona Gurzu

Keyword(s):

Pancreatic Cancer ◽

Tumor Cells ◽

Surgical Intervention ◽

Chylous Ascites ◽

Distal Portion ◽

Ductal Adenocarcinoma ◽

Lymph Vessels ◽

Lymphangiosis Carcinomatosa ◽

Ductal Pancreatic Adenocarcinoma ◽

Tumor Emboli

AbstractChylous ascites represents a relatively uncommon condition. In this paper, we present a case of chyloperitoneum associated with pancreatic ductal adenocarcinoma (PDAC) and a review of literature regarding chylous ascites. A 76-year-old male patient was admitted in emergency department with acute abdomen. A pancreatic cancer was suspected. Subtotal spleno-pancreatectomy, for a nodular mass infiltrating the mild and distal portion of the pancreas, was necessary. During surgical intervention in the peritoneal cavity, a moderate quantity of whitish and thick consistency fluid with milk-like appearance was observed to be accumulated. After examination of the fluid, chyloperitoneum was diagnosed. The histologic examination showed a PDAC, with multiple emboli in lymph vessels, with tumor cells with plasmacytoid morphology, diagnosed as lymphangiosis carcinomatosa. The patient died at 3 weeks after surgical intervention. In patients with pancreatic cancer and chylous ascites, suspicion of tumor-related blockage of the lymphatic flow should be suspected. Prognosis of PDAC should be evaluated not only based on the number of lymph node metastases, but also considering the number of lymph vessels with tumor emboli and the architecture of tumor cells. This is the first reported case of a PDAC with plasmacytoid morphology of lymphangiosis carcinomatosa.

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Clinical Perspective on Proteomic and Glycomic Biomarkers for Diagnosis, Prognosis, and Prediction of Pancreatic Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22052655 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2655

Author(s):

Randa G. Hanna-Sawires ◽

Jorinde H. Schiphuis ◽

Manfred Wuhrer ◽

Hans F. A. Vasen ◽

Monique E. van Leerdam ◽

...

Keyword(s):

Pancreatic Cancer ◽

Surgical Techniques ◽

Protein Glycosylation ◽

Ductal Adenocarcinoma ◽

Careful Study ◽

Prognosis And Prediction ◽

Prognostic Stratification ◽

Neo Adjuvant Chemotherapy ◽

New Biomarkers ◽

Study Designs

Pancreatic ductal adenocarcinoma (PDAC) is known as a highly aggressive malignant disease. Prognosis for patients is notoriously poor, despite improvements in surgical techniques and new (neo)adjuvant chemotherapy regimens. Early detection of PDAC may increase the overall survival. It is furthermore foreseen that precision medicine will provide improved prognostic stratification and prediction of therapeutic response. In this review, omics-based discovery efforts are presented that aim for novel diagnostic and prognostic biomarkers of PDAC. For this purpose, we systematically evaluated the literature published between 1999 and 2020 with a focus on protein- and protein-glycosylation biomarkers in pancreatic cancer patients. Besides genomic and transcriptomic approaches, mass spectrometry (MS)-based proteomics and glycomics of blood- and tissue-derived samples from PDAC patients have yielded new candidates with biomarker potential. However, for reasons discussed in this review, the validation and clinical translation of these candidate markers has not been successful. Consequently, there has been a change of mindset from initial efforts to identify new unimarkers into the current hypothesis that a combination of biomarkers better suits a diagnostic or prognostic panel. With continuing development of current research methods and available techniques combined with careful study designs, new biomarkers could contribute to improved detection, prognosis, and prediction of pancreatic cancer.

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High Clinical Value of Liquid Biopsy to Detect Circulating Tumor Cells and Tumor Exosomes in Pancreatic Ductal Adenocarcinoma Patients Eligible for Up-Front Surgery

Cancers ◽

10.3390/cancers11111656 ◽

2019 ◽

Vol 11 (11) ◽

pp. 1656 ◽

Cited By ~ 12

Author(s):

Etienne Buscail ◽

Catherine Alix-Panabières ◽

Pascaline Quincy ◽

Thomas Cauvin ◽

Alexandre Chauvet ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Liquid Biopsy ◽

Neoadjuvant Treatment ◽

Digital Pcr ◽

Portal Blood ◽

Ductal Adenocarcinoma ◽

Clinical Value ◽

Liquid Biopsies

Purpose: Expediting the diagnosis of pancreatic ductal adenocarcinoma (PDAC) would benefit care management, especially for the start of treatments requiring histological evidence. This study evaluated the combined diagnostic performance of circulating biomarkers obtained by peripheral and portal blood liquid biopsy in patients with resectable PDAC. Experimental design: Liquid biopsies were performed in a prospective translational clinical trial (PANC-CTC #NCT03032913) including 22 patients with resectable PDAC and 28 noncancer controls from February to November 2017. Circulating tumor cells (CTCs) were detected using the CellSearch® method or after RosetteSep® enrichment combined with CRISPR/Cas9-improved KRAS mutant alleles quantification by droplet digital PCR. CD63 bead-coupled Glypican-1 (GPC1)-positive exosomes were quantified by flow cytometry. Results: Liquid biopsies were positive in 7/22 (32%), 13/22 (59%), and 14/22 (64%) patients with CellSearch® or RosetteSep®-based CTC detection or GPC1-positive exosomes, respectively, in peripheral and/or portal blood. Liquid biopsy performance was improved in portal blood only with CellSearch®, reaching 45% of PDAC identification (5/11) versus 10% (2/22) in peripheral blood. Importantly, combining CTC and GPC1-positive-exosome detection displayed 100% of sensitivity and 80% of specificity, with a negative predictive value of 100%. High levels of GPC1+-exosomes and/or CTC presence were significantly correlated with progression-free survival and with overall survival when CTC clusters were found. Conclusion: This study is the first to evaluate combined CTC and exosome detection to diagnose resectable pancreatic cancers. Liquid biopsy combining several biomarkers could provide a rapid, reliable, noninvasive decision-making tool in early, potentially curable pancreatic cancer. Moreover, the prognostic value could select patients eligible for neoadjuvant treatment before surgery. This exploratory study deserves further validation.

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Detection of Circulating Tumor Cells Using Negative Enrichment Immunofluorescence and an In Situ Hybridization System in Pancreatic Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms18040622 ◽

2017 ◽

Vol 18 (4) ◽

pp. 622 ◽

Cited By ~ 16

Author(s):

Yu Xu ◽

Tai Qin ◽

Jing Li ◽

Xiuchao Wang ◽

Chuntao Gao ◽

...

Keyword(s):

Pancreatic Cancer ◽

In Situ Hybridization ◽

Tumor Cells ◽

Circulating Tumor Cells

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Microfluidic Chip-Based Cancer Diagnosis and Prediction of Relapse by Detecting Circulating Tumor Cells and Circulating Cancer Stem Cells

Cancers ◽

10.3390/cancers13061385 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1385

Author(s):

Hyeon-Yeol Cho ◽

Jin-Ha Choi ◽

Joungpyo Lim ◽

Sang-Nam Lee ◽

Jeong-Woo Choi

Keyword(s):

Stem Cells ◽

Cancer Stem Cells ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Metastatic Cancer ◽

Cancer Prognosis ◽

Optical Biosensors ◽

Diagnosis And Prognosis ◽

Noise Factors ◽

Prediction Of Relapse

Detecting circulating tumor cells (CTCs) has been considered one of the best biomarkers in liquid biopsy for early diagnosis and prognosis monitoring in cancer. A major challenge of using CTCs is detecting extremely low-concentrated targets in the presence of high noise factors such as serum and hematopoietic cells. This review provides a selective overview of the recent progress in the design of microfluidic devices with optical sensing tools and their application in the detection and analysis of CTCs and their small malignant subset, circulating cancer stem cells (CCSCs). Moreover, discussion of novel strategies to analyze the differentiation of circulating cancer stem cells will contribute to an understanding of metastatic cancer, which can help clinicians to make a better assessment. We believe that the topic discussed in this review can provide brief guideline for the development of microfluidic-based optical biosensors in cancer prognosis monitoring and clinical applications.

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