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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
- Source :
- Cancers, Cancers, MDPI, 2019, 11 (11), pp.1656. ⟨10.3390/cancers11111656⟩, Volume 11, Issue 11, Cancers, 2019, 11 (11), pp.1656. ⟨10.3390/cancers11111656⟩, Cancers, Vol 11, Iss 11, p 1656 (2019)
- Publication Year :
- 2019
- Publisher :
- HAL CCSD, 2019.
-
Abstract
- 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&reg<br />method or after RosetteSep&reg<br />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&reg<br />or RosetteSep&reg<br />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&reg<br />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.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_specialty
endocrine system diseases
pancreatic cancer
[SDV.CAN]Life Sciences [q-bio]/Cancer
exosomes
circulating tumor cells
medicine.disease_cause
lcsh:RC254-282
Exosome
Article
Flow cytometry
03 medical and health sciences
0302 clinical medicine
Circulating tumor cell
[SDV.CAN] Life Sciences [q-bio]/Cancer
Pancreatic cancer
Medicine
Digital polymerase chain reaction
Liquid biopsy
medicine.diagnostic_test
liquid biopsy
business.industry
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
digestive system diseases
3. Good health
Surgery
Clinical trial
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
KRAS
business
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Database :
- OpenAIRE
- Journal :
- Cancers, Cancers, MDPI, 2019, 11 (11), pp.1656. ⟨10.3390/cancers11111656⟩, Volume 11, Issue 11, Cancers, 2019, 11 (11), pp.1656. ⟨10.3390/cancers11111656⟩, Cancers, Vol 11, Iss 11, p 1656 (2019)
- Accession number :
- edsair.doi.dedup.....479ed404b70383ecfe97d741b3e157e1