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

// Adam E. Frampton 1, 2, * , Mireia Mato Prado 2, * , Elena Lopez-Jimenez 2 , Ana Belen Fajardo-Puerta 1 , Zaynab A.R. Jawad 1 , Phillip Lawton 2 , Elisa Giovannetti 3, 4 , Nagy A. Habib 1 , Leandro Castellano 2, 5 , Justin Stebbing 2, # , Jonathan Krell 2, # and Long R. Jiao 1, # 1 HPB Surgical Unit, Department of Surgery and Cancer, Imperial College, London, UK 2 Division of Cancer, Department of Surgery and Cancer, Imperial College, London, UK 3 Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, Amsterdam, The Netherlands 4 Cancer Pharmacology Lab, AIRC Start-Up Unit, University of Pisa, Pisa, Italy 5 University 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 Correspondence to: Long R. Jiao, email: l.jiao@imperial.ac.uk Keywords: Glypican-1 (GPC1); pancreatic ductal adenocarcinoma (PDAC); exosome; biomarker; tumor size Received: October 28, 2017 Accepted: March 02, 2018 Published: April 10, 2018 ABSTRACT 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 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.