Glypican-1 is enriched in circulating-exosomes in pancreatic cancer and correlates with tumor burden
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Adam E. Frampton1,2,*, Mireia Mato Prado2,*, Elena López-Jiménez2, Ana Belen Fajardo-Puerta1, Zaynab A.R. Jawad1, Phillip Lawton2, Elisa Giovannetti3,4, Nagy A. Habib1, Leandro Castellano2,5, Justin Stebbing2,#, Jonathan Krell2,# and Long R. Jiao1,#
1HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, London, UK
2Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK
3Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands
4Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy
5University of Sussex, School of Life Sciences, John Maynard Smith Building, Falmer, Brighton, UK
*These authors share co-first authorship
#These authors share co-senior authorship
Long R. Jiao, email: [email protected]
Keywords: Glypican-1 (GPC1); pancreatic ductal adenocarcinoma (PDAC); exosome; biomarker; tumor size
Received: October 28, 2017 Accepted: March 02, 2018 Published: April 10, 2018
Background: Glypican-1 (GPC1) is expressed in pancreatic ductal adenocarcinoma (PDAC) cells and adjacent stromal fibroblasts. Recently, GPC1 circulating exosomes (crExos) have been shown to be able to detect early stages of PDAC. In this study, we 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 higher 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.
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