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

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.

Download Full-text

Liquid biopsy in pancreatic ductal adenocarcinoma: current status of circulating tumor cells and circulating tumorDNA

Molecular Oncology ◽

10.1002/1878-0261.12537 ◽

2019 ◽

Vol 13 (8) ◽

pp. 1623-1650 ◽

Cited By ~ 13

Author(s):

Jee‐Soo Lee ◽

Sung Sup Park ◽

Young Kyung Lee ◽

Jeffrey A. Norton ◽

Stefanie S. Jeffrey

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Liquid Biopsy ◽

Current Status ◽

Ductal Adenocarcinoma

Download Full-text

A model for the detection of pancreatic ductal adenocarcinoma circulating tumor cells

Journal of Biological Methods ◽

10.14440/jbm.2018.250 ◽

2018 ◽

Vol 5 (3) ◽

pp. 97 ◽

Cited By ~ 3

Author(s):

Matthew S. Alexander ◽

Brianne R. O'Leary ◽

Devon Moose ◽

Juan Du ◽

Michael D. Henry ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Ductal Adenocarcinoma

Download Full-text

Circulating Tumor Cells Expressing Markers of Tumor-Initiating Cells Predict Poor Survival and Cancer Recurrence in Patients with Pancreatic Ductal Adenocarcinoma

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-16-1467 ◽

2016 ◽

Vol 23 (11) ◽

pp. 2681-2690 ◽

Cited By ~ 40

Author(s):

Katherine E. Poruk ◽

Amanda L. Blackford ◽

Matthew J. Weiss ◽

John L. Cameron ◽

Jin He ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cancer Recurrence ◽

Ductal Adenocarcinoma ◽

Tumor Initiating Cells ◽

Poor Survival

Download Full-text

Detection of Circulating Tumor Cells in Resectable Pancreatic Ductal Adenocarcinoma: A Prospective Evaluation as a Prognostic Marker

Frontiers in Oncology ◽

10.3389/fonc.2020.616440 ◽

2021 ◽

Vol 10 ◽

Author(s):

Byeong Geun Song ◽

Wooil Kwon ◽

Hyemin Kim ◽

Eun Mi Lee ◽

Young Min Han ◽

...

Keyword(s):

Portal Vein ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Prognostic Marker ◽

Peripheral Blood ◽

Early Stage ◽

Portal Blood ◽

Ductal Adenocarcinoma ◽

Venous Blood Flow ◽

Porous Filter

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.

Download Full-text

Molecular characterization of circulating tumor cells in pancreatic ductal adenocarcinoma: potential diagnostic and prognostic significance in clinical practice

HepatoBiliary Surgery and Nutrition ◽

10.21037/hbsn-20-383 ◽

2021 ◽

Vol 0 (0) ◽

pp. 0-0

Author(s):

Xudong Zhao ◽

Yongsu Ma ◽

Xiu Dong ◽

Zhengkui Zhang ◽

Xiaodong Tian ◽

...

Keyword(s):

Clinical Practice ◽

Pancreatic Ductal Adenocarcinoma ◽

Tumor Cells ◽

Molecular Characterization ◽

Circulating Tumor Cells ◽

Prognostic Significance ◽

Ductal Adenocarcinoma

Download Full-text

Detection of AR-V7 in Liquid Biopsies of Castrate Resistant Prostate Cancer Patients: A Comparison of AR-V7 Analysis in Circulating Tumor Cells, Circulating Tumor RNA and Exosomes

Cells ◽

10.3390/cells8070688 ◽

2019 ◽

Vol 8 (7) ◽

pp. 688 ◽

Cited By ~ 8

Author(s):

Mohammed Nimir ◽

Yafeng Ma ◽

Sarah A. Jeffreys ◽

Thomas Opperman ◽

Francis Young ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Digital Pcr ◽

Liquid Biopsies ◽

Tumor Biopsy ◽

Highly Sensitive ◽

Castrate Resistant Prostate Cancer ◽

Castrate Resistant

Detection of androgen receptor (AR) variant 7 (AR-V7) is emerging as a clinically important biomarker in castrate resistant prostate cancer (CRPC). Detection is possible from tumor tissue, which is often inaccessible in the advanced disease setting. With recent progress in detecting AR-V7 in circulating tumor cells (CTCs), circulating tumor RNA (ctRNA) and exosomes from prostate cancer patients, liquid biopsies have emerged as an alternative to tumor biopsy. Therefore, it is important to clarify whether these approaches differ in sensitivity in order to achieve the best possible biomarker characterization for the patient. In this study, blood samples from 44 prostate cancer patients were processed for CTCs and ctRNA with subsequent AR-V7 testing, while exosomal RNA was isolated from 16 samples and tested. Detection of AR and AR-V7 was performed using a highly sensitive droplet digital PCR-based assay. AR and AR-V7 RNA were detectable in CTCs, ctRNA and exosome samples. AR-V7 detection from CTCs showed higher sensitivity and has proven specificity compared to detection from ctRNA and exosomes. Considering that CTCs are almost always present in the advanced prostate cancer setting, CTC samples should be considered the liquid biopsy of choice for the detection of this clinically important biomarker.

Download Full-text

Doublecortin-Like Kinase 1 Is Elevated Serologically in Pancreatic Ductal Adenocarcinoma and Widely Expressed on Circulating Tumor Cells

PLoS ONE ◽

10.1371/journal.pone.0118933 ◽

2015 ◽

Vol 10 (2) ◽

pp. e0118933 ◽

Cited By ~ 26

Author(s):

Dongfeng Qu ◽

Jeremy Johnson ◽

Parthasarathy Chandrakesan ◽

Nathaniel Weygant ◽

Randal May ◽

...

Keyword(s):

Pancreatic Ductal Adenocarcinoma ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Ductal Adenocarcinoma

Download Full-text

The role of liquid biopsies in prostate cancer management

Lab on a Chip ◽

10.1039/d1lc00485a ◽

2021 ◽

Author(s):

Chi-Ju Kim ◽

Liang Dong ◽

Sarah Amend ◽

Yoon-Kyoung Cho ◽

Kenneth Pienta

Keyword(s):

Prostate Cancer ◽

Tumor Cells ◽

Circulating Tumor Cells ◽

Cancer Diagnosis ◽

Liquid Biopsy ◽

Liquid Biopsies ◽

Cancer Management ◽

The Common ◽

Prostate Cancer Management

Liquid biopsy has emerged as a complement to invasive tissue biopsy to guide cancer diagnosis and treatment. The common liquid biopsy biomarkers are circulating tumor cells (CTCs), extracellular vesicles (EVs),...

Download Full-text