Vimentin-positive circulating tumor cells as a biomarker for diagnosis and treatment monitoring in patients with pancreatic cancer
Vimentin-positive circulating tumor cells as a biomarker for diagnosis and treatment monitoring in patients with pancreatic cancer
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波形蛋白阳性循环肿瘤细胞作为胰腺癌患者诊断和治疗监测的生物标志物
DOI：
10.1016/j.canlet.2019.03.009
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发表时间：
2019-01-01
期刊：
影响因子：
9.7
通讯作者：
Bai, Xueli
中科院分区：
文献类型：
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作者：
Wei, Tao;Zhang, Xiaoyu;Bai, Xueli
循环肿瘤细胞（CTCs）的鉴定依赖于上皮肿瘤细胞标志物。在本研究中，我们旨在确定细胞表面波形蛋白是否可作为一种生物标志物用于分离胰腺导管腺癌（PDAC）中的CTCs。波形蛋白被确定在间充质表型胰腺肿瘤细胞表面高表达。通过微流控检测法富集CTCs后，在76%的胰腺导管腺癌患者（76/100）中检测到波形蛋白（+）CTCs。两个波形蛋白（+）CTCs的临界值可区分胰腺导管腺癌患者和健康个体。波形蛋白（+）CTCs与糖类抗原19 - 9联合具有良好的诊断效能，曲线下面积为0.968。波形蛋白（+）CTCs计数与接受切除手术的患者的肿瘤负荷变化相关。在对治疗有反应的受试者中，化疗后观察到CTCs计数显著降低。术前较高的CTCs计数与较短的无复发生存期相关。综上所述，波形蛋白（+）CTCs可能是胰腺癌的一种可靠生物标志物。间充质CTCs的富集补充了捕获上皮CTCs的策略，从而能够更全面地探究胰腺导管腺癌中CTCs的生物学特性和临床意义。
The identification of circulating tumor cells (CTCs) relies on epithelial tumor cell markers. In the present study, we aimed to determine whether cell-surface vimentin could be a biomarker to isolate CTCs in pancreatic ductal adenocarcinoma (PDAC). Vimentin was identified as highly expressed on the surface of mesenchymal-phenotype pancreatic tumor cells. Vimentin(+) CTCs were detected in 76% of patients with PDAC (76/100) using CTCs enriched via a microfluidic assay. A cut-off value of two vimentin(+) CTCs distinguished patients with PDAC from healthy individuals. Combined vimentin(+ )CTCs and Carbohydrate antigen 19-9 provided favorable diagnostic potency, with an area under the curve of 0.968. Vimentin(+) CTCs counts correlated with the change in tumor burden for patients undergoing resection. Significantly reduced CTC counts were observed after chemotherapy in subjects that responded to treatment. Preoperatively higher CTCs counts correlated with shortened recurrence-free survival. Taken together, vimentin(+) CTCs could be a reliable biomarker in pancreatic cancer. The enrichment of mesenchymal CTCs complements the strategy of capturing epithelial CTCs, allowing a more thorough interrogation of the biology and clinical significance of CTCs in PDAC.