Glypican-1 is enriched in circulating-exosomes in pancreatic cancer and correlates with tumor burden.
Glypican-1 is enriched in circulating-exosomes in pancreatic cancer and correlates with tumor burden.
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DOI：
10.18632/oncotarget.24873
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发表时间：
2018-04-10
期刊：
影响因子：
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通讯作者：
Jiao LR
中科院分区：
文献类型：
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作者：
Frampton AE;Prado MM;López-Jiménez E;Fajardo-Puerta AB;Jawad ZAR;Lawton P;Giovannetti E;Habib NA;Castellano L;Stebbing J;Krell J;Jiao LR
Glypican-1 (GPC1) 在胰腺导管腺癌细胞 (PDAC) 和邻近的基质成纤维细胞中表达。最近，GPC1 循环外泌体 (crExos) 已被证明能够检测 PDAC 的早期阶段。在本研究中，我们研究了 crExos GPC1 作为 PDAC 生物标志物的有用性。在胰腺切除术之前从患有良性胰腺疾病 (n = 16) 和 PDAC (n = 27) 的患者中获取血浆，并通过超速离心分离 crExos。从手术标本中提取蛋白质（邻近正常胰腺，n = 13；PDAC，n = 17）。使用酶联免疫吸附测定 (ELISA) 测量 GPC1 水平。正常胰腺和PDAC组织中GPC1水平无显着差异。在比较匹配对时也是如此。然而，与源肿瘤相比，PDAC crExos (n = 11) 中的 GPC1 水平较高 (n = 11; 97 ± 54 vs. 20.9 ± 12.3 pg/mL; P < 0.001)。此外，具有高 GPC1 表达的 PDAC 往往具有较高 GPC1 水平的 crExos。尽管有这些发现，我们仍无法使用 crExos GPC1 水平区分 PDAC 和良性胰腺疾病。有趣的是，我们发现在匹配的术前和术后血浆样本中，PDAC 手术切除后 crExos GPC1 水平显着下降（n = 11 vs. 11；97 ± 54 vs. 77.8 ± 32.4 pg/mL；P = 0.0428）。此外，我们发现 crExos GPC1 水平高的患者具有显着更大的 PDAC（> 4 cm；P = 0.012）。高 GPC1 crExos 可能能够确定 PDAC 肿瘤大小和疾病负担。然而，需要进一步努力使用更大的 PDAC 患者群体来阐明其作为诊断和/或预后生物标志物的作用。
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. 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). 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). 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.