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

Frampton, Adam E, Prado, Mireia Mato, López-Jiménez, Elena, Fajardo-Puerta, Ana Belen, Jawad, Zaynab A R, Lawton, Phillip, Giovannetti, Elisa, Habib, Nagy A, Castellano, Leandro, Stebbing, Justin, Krell, Jonathan and Jiao, Long R (2018) Glypican-1 is enriched in circulating-exosomes in pancreatic cancer and correlates with tumor burden. Oncotarget, 9 (27). pp. 19006-19013. ISSN 1949-2553

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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 ( = 16) and PDAC ( = 27) prior to pancreatectomy, and crExos were isolated by ultra-centrifugation. Protein was extracted from surgical specimens (adjacent normal pancreas, = 13; and PDAC, = 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 ( = 11), compared to the source tumors ( = 11; 97 ± 54 vs. 20.9 ± 12.3 pg/mL; < 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 ( = 11 vs. 11; 97 ± 54 vs. 77.8 ± 32.4 pg/mL; = 0.0428). Furthermore, we found that patients with high crExos GPC1 levels have significantly larger PDACs (>4 cm; = 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.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Leandro Castellano
Date Deposited: 15 Jun 2018 08:17
Last Modified: 02 Jul 2019 15:31
URI: http://sro.sussex.ac.uk/id/eprint/76513

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