Extracellular Vesicle-Based Detection of Pancreatic Cancer
Open Access
- 23 July 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Cell and Developmental Biology
Abstract
Due to a grim prognosis, there is an urgent need to detect pancreatic ductal adenocarcinoma (PDAC) prior to metastasis. However, reliable diagnostic imaging methods or biomarkers for PDAC or its precursor lesions are still scarce. ADAM8, a metalloprotease-disintegrin, is highly expressed in PDAC tissue and negatively correlates with patient survival. The aim of our study was to determine the ability of ADAM8-positive extracellular vesicles (EVs) and cargo microRNAs (miRNAs) to discriminate precursor lesions or PDAC from healthy controls. In order to investigate enrichment of ADAM8 on EVs, these were isolated from serum of patients with PDAC (n = 52), precursor lesions (n = 7) and healthy individuals (n = 20). Nanoparticle Tracking Analysis and electron microscopy indicated successful preparation of EVs that were analyzed for ADAM8 by FACS. Additionally, EV cargo analyses of miRNAs from the same serum samples revealed the presence of miR-720 and miR-451 by qPCR and was validated in 20 additional PDAC samples. Statistical analyses included Wilcoxon rank test and ROC curves. FACS analysis detected significant enrichment of ADAM8 in EVs from patients with PDAC or precursor lesions compared to healthy individuals (p = 0.0005). ADAM8-dependent co-variates, miR-451 and miR-720 were also diagnostic, as patients with PDAC had significantly higher serum levels of miR-451 and lower serum levels of miR-720 than healthy controls and reached high sensitivity and specificity (AUC = 0.93 and 1.00, respectively) to discriminate PDAC from healthy control. Thus, detection of ADAM8-positive EVs and related cargo miR-720 and miR-451 may constitute a specific biomarker set for screening individuals at risk for PDAC.Funding Information
- Deutsche Forschungsgemeinschaft (BA-1606/4-1)
This publication has 23 references indexed in Scilit:
- Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypesProceedings of the National Academy of Sciences of the United States of America, 2016
- Glypican-1 identifies cancer exosomes and detects early pancreatic cancerNature, 2015
- Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesiclesOncotarget, 2015
- ADAM8 as a drug target in pancreatic cancerNature Communications, 2015
- Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular VesiclesAnnual Review of Cell and Developmental Biology, 2014
- Establishment of robust controls for the normalization of miRNA expression in neuroendocrine tumors of the ileum and pancreasEndocrine, 2014
- A role for miR-155 in enabling tumor-infiltrating innate immune cells to mount effective antitumor responses in miceBlood, 2013
- Systemic presence and tumor-growth promoting effect of ovarian carcinoma released exosomesCancer Letters, 2009
- ADAM8 expression is associated with increased invasiveness and reduced patient survival in pancreatic cancerJournal of Cellular and Molecular Medicine, 2007
- Isolation and Characterization of Exosomes from Cell Culture Supernatants and Biological FluidsCurrent Protocols in Cell Biology, 2006