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

Abstract

BackgroundGlypican-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.MethodsPlasma 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).ResultsThere 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).ConclusionsHigh 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.

Multiple antibodies identify glypican-1 associated with exosomes from pancreatic cancer cells and serum from patients with pancreatic cancer

“…As such, exosomes from the serum of patients emerged as an attractive approach to possibly detect cancerous lesions and monitor and predict outcome of cancer patients. Several studies have reproduced our original findings related to enrichment of GPC1 in cancer exosomes, including in breast cancer exosomes, colorectal, esophageal and pancreas cancer [2][3][4][5]8,[18][19][20] (Table 1). Additionally, most of these reports show that such enrichment of GPC1 in exosomes can serve as biomarker.…”

“…In the last two years, GPC1 detection on cancer exosomes has been demonstrated by several different independent studies. Such validation included breast cancer cellsderived exosomes and colorectal and esophageal cancer-derived exosomes, in addition to exosomes analyzed from pancreatic cancer cases [2][3][4][5]8,14,[18][19][20] (Table 1). Despite employing different methodologies and approaches, GPC1 was reported as elevated in exosomes of patients with different cancer types.…”

“…Here we provide a detailed methodology, in a stepwise manner, to accompany the findings reported here ( Table 4). Collectively, 6 different antibodies have been described to identify GPC1 positive cancer exosomes by different laboratories [2][3][4][5]8,14,[18][19][20] . We look forward to a productive scientific discourse on the utility of GPC1 positive cancer exosomes in the detection of pancreatic cancer, among others.…”

Comprehensive genomic profile of cholangiocarcinomas in China

“…TMB is correlated with clinical outcome in multiple cancer types treated with CPI (65,66). Previous studies indicated that TMB levels correlated with gene mutations in tumors (25,40,67,68). TMB-H has been reported to correlate with the generation of neoantigens and potential clinical responses to immunotherapies (69).…”

Familial Pancreatic Cancer

“…Newly found biomarkers such as AHNAK2 or THBS2, which are potentially successful diagnostic markers, need to be involved in studies to show their effects in screening programs [84,85,86]. Additionally, biomarkers like Glypican-1, CD63, and miR-451a exosomes seem to be promising [87,88,89]. Nevertheless, in the development of successful biomarkers, it needs to be noted that predispositions such as chronic pancreatitis and pancreatic cancer may have different genetic abnormalities [90].…”