Glypican-1 is enriched in circulating-exosomes in pancreatic cancer and correlates with tumor burden
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Author(s)
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.
(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.
Date Issued
2018-04-10
Date Acceptance
2018-03-02
Citation
Oncotarget, 2018, 9, pp.19006-19013
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.
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
Royal College of Surgeons Edinburgh
Grant Number
SRG/17/100
Subjects
Glypican-1 (GPC1)
biomarker
exosome
pancreatic ductal adenocarcinoma (PDAC)
tumor size
Publication Status
Published