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

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posted on 2023-06-09, 13:46 authored by Adam E Frampton, Mireia Mato Prado, Elena López-Jiménez, Ana Belen Fajardo-Puerta, Zaynab A R Jawad, Phillip Lawton, Elisa Giovannetti, Nagy A Habib, Leandro CastellanoLeandro Castellano, Justin Stebbing, Jonathan Krell, Long R Jiao
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Oncotarget

ISSN

1949-2553

Publisher

Impact Journals

Issue

27

Volume

9

Page range

19006-19013

Department affiliated with

  • Biochemistry Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2018-06-15

First Open Access (FOA) Date

2018-06-15

First Compliant Deposit (FCD) Date

2018-06-15

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