CD63-GPC1-Positive Exosomes Coupled with CA19-9 Offer Good Diagnostic Potential for Resectable Pancreatic Ductal Adenocarcinoma
CD63-GPC1-Positive Exosomes Coupled with CA19-9 Offer Good Diagnostic Potential for Resectable Pancreatic Ductal Adenocarcinoma
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DOI：
10.1016/j.tranon.2019.07.009
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发表时间：
2019-11-01
影响因子：
5
通讯作者：
Dabernat, Sandrine
中科院分区：
文献类型：
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作者：
Buscail, Etienne;Chauvet, Alexandre;Dabernat, Sandrine
肿瘤释放的胞外囊泡(EV)含有肿瘤特异性物质，使它们有别于健康的EV，并使它们有资格作为循环生物标记物。Glypical1(GPC1)-作为液体活检要素的正外切体相关性仍有争议。我们开展了一项前瞻性研究，以量化接受前期手术的胰腺导管腺癌(PDAC)患者血清中GPC1阳性外切体，并与包括无癌病史患者和表现为胰腺癌前期病变的患者在内的对照组进行比较。血清富含EVS，抗CD63偶联磁珠拖拉外切体。流式细胞仪检测PDAC组GPC1阳性珠粒百分率明显高于对照组。联合外周血和门静脉血的诊断准确率达78%(敏感性%，特异性90%)。结合超声引导细针抽吸(EUS-FNA)，阴性预测值为80%，而仅EUS-FNA的阴性预测值为33%。由于外周血中GPC1阳性外切体患者的无瘤存活率降低，这种方法作为现有诊断工具的配套测试在临床上是相关的。
Tumor-released extracellular vesicles (EVs) contain tumor-specific cargo distinguishing them from healthy EVs, and making them eligible as circulating biomarkers. Glypican 1 (GPC1)-positive exosome relevance as liquid biopsy elements is still debated. We carried out a prospective study to quantify GPC1-positive exosomes in sera from pancreatic ductal adenocarcinoma (PDAC) patients undergoing up-front surgery, as compared to controls including patients without cancer history and patients displaying pancreatic preneoplasic lesions. Sera were enriched in EVs, and exosomes were pulled down with anti-CD63 coupled magnetic beads. GPC1-positive bead percentages determined by flow cytometry were significantly higher in PDAC than in the control group. Diagnosis accuracy reached 78% (sensitivity 64% and specificity 90%), when results from peripheral and portal blood were combined. In association with echo-guided-ultrasound-fine-needle-aspiration (EUS-FNA) negative predictive value was 80% as compared to 33% for EUS-FNA only. This approach is clinically relevant as a companion test to the already available diagnostic tools, since patients with GPC1-positive exosomes in peripheral blood showed decreased tumor free survival.