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Glypican-1 is enriched in circulating-exosomes in pancreatic cancer and correlates with tumor burden

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Title: Glypican-1 is enriched in circulating-exosomes in pancreatic cancer and correlates with tumor burden
Authors: Frampton, AE
Mato Prado, M
Lopez Jimenez, ME
Fajardo Puerta, AB
Jawad, ZR
Lawton, P
Giovannetti, E
Habib, N
Castellano, L
Stebbing, J
Krell, J
Jiao, L
Item Type: Journal Article
Abstract: Background: Glypican-1 (GPC1) is expressed in pancreatic ductal adenocarcinoma (PDAC) cells and adjacent stroma fibroblasts. Recently, GPC1 circulating exosomes (crExos) have been shown to be able to detect early stages of PDAC. This study investigated the usefulness of crExos GPC1 as a biomarker for PDAC. Methods: Plasma was obtained from patients with benign pancreatic disease ( n = 16) and PDAC ( n = 27) prior to pancreatectomy, and crExos were isolated by ultra-centrifugation. Protein was extracted from surgical specimens (adjacent normal pancreas, n = 13; and PDAC, n = 17). GPC1 levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: There was no significant difference in GPC1 levels between normal pancreas and PDAC tissues. This was also true when comparing matched pairs. However, GPC1 levels were enriched in PDAC crExos ( n = 11), compared to the source tumors ( n = 11; 97 ± 54 vs. 20.9 ± 12.3 pg/mL; P < 0.001). In addition, PDACs with high GPC1 expression tended to have crExos with high GPC1 levels. Despite these findings, we were unable to distinguish PDAC from benign pancreatic disease using crExos GPC1 levels. Interestingly, we found that in matched pre and post-operative plasma samples there was a significant drop in crExos GPC1 levels after surgical resection for PDAC ( n = 11 vs. 11; 97 ± 54 vs. 77.8 ± 32.4 pg/mL; P = 0.0428). Furthermore, we found that patients with high crExos GPC1 levels have significantly larger PDACs (>4 cm; P = 0.012). Conclusions: High GPC1 crExos may be able to determine PDAC tumor size and disease burden. However, further efforts are needed to elucidate its role as a diagnostic and/or prognostic biomarker using larger cohorts of PDAC patients.
Issue Date: 10-Apr-2018
Date of Acceptance: 2-Mar-2018
URI: http://hdl.handle.net/10044/1/57827
DOI: https://dx.doi.org/10.18632/oncotarget.24873
ISSN: 1949-2553
Publisher: Impact Journals
Start Page: 19006
End Page: 19013
Journal / Book Title: Oncotarget
Volume: 9
Copyright Statement: © Frampton et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor/Funder: Royal College of Surgeons Edinburgh
Funder's Grant Number: SRG/17/100
Keywords: Glypican-1 (GPC1)
biomarker
exosome
pancreatic ductal adenocarcinoma (PDAC)
tumor size
Publication Status: Published
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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