Sensitive detection of viable circulating tumor cells using a novel conditionally telomerase-selective replicating adenovirus in non-small cell lung cancer patients.
Sensitive detection of viable circulating tumor cells using a novel conditionally telomerase-selective replicating adenovirus in non-small cell lung cancer patients.
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DOI：
10.18632/oncotarget.16818
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发表时间：
2017-05-23
期刊：
影响因子：
--
通讯作者：
Takahashi K
中科院分区：
文献类型：
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作者：
Togo S;Katagiri N;Namba Y;Tulafu M;Nagahama K;Kadoya K;Takamochi K;Oh S;Suzuki K;Sakurai F;Mizuguchi H;Urata Y;Takahashi K
循环肿瘤细胞（CTC）在癌症患者的临床结局中起着至关重要的作用。使用针对捕获的CTC中的上皮细胞粘附分子（EpCAM）的抗体检测非小细胞肺癌（NSCLC）具有低灵敏度;上皮标志物的损失导致低估具有间充质表型的CTC。我们提出了一种新的方法来检测可行的CTC，包括上皮-间质转化状态（EMT-CTC），使用新的端粒酶特异性复制选择性腺病毒（OBP-1101），TelomeScan F35。收集123例NSCLC患者的外周静脉血样本和临床病理资料。CTC检测的敏感性为69.1%，其中I、II、III和IV期患者的敏感性分别为59.6%、40.0%、85.7%和75.0%。在EMT-CTC样品中，46%为波形蛋白阳性，39.0%的非EMT-CTC样品为EpCAM阳性。基线时EMT-CTC检测阳性的患者对化疗的反应较差（P = 0.025），无进展生存期缩短（EMT-CTC阳性vs阴性：193 ± 47天vs 388 ± 47天）。天，P = 0.040）与那些测试阴性的相比。TelomeScan F35是一种高灵敏度的CTC检测系统，将成为NSCLC患者早期诊断的有用筛查工具。间质表型CTC是NSCLC患者化疗疗效的关键指标。
Circulating tumor cells (CTCs) have a crucial role in the clinical outcome of cancer patients. Detection of non-small cell lung cancer (NSCLC) using an antibody against epithelial cell adhesion molecule (EpCAM) in captured CTCs has low sensitivity; the loss of epithelial markers leads to underestimation of CTCs with mesenchymal phenotype. We propose a new approach for detection of viable CTCs, including those with epithelial-mesenchymal transition status (EMT-CTCs), using the new telomerase-specific replication-selective adenovirus (OBP-1101), TelomeScan F35. Peripheral venous blood samples and clinicopathological data were collected from 123 NSCLC patients. The sensitivity of CTC detection was 69.1%, and for patients with stage I, II, III and IV, it was 59.6%, 40.0%, 85.7%, and 75.0%, respectively. Among the EMT-CTC samples, 46% were vimentin positive and 39.0% of non-EMT-CTC samples were EpCAM positive. Patients testing positive for EMT-CTCs at baseline had poor response to chemotherapy (P = 0.025) and decreased progression-free survival (EMT-CTC positive vs. negative: 193 ± 47 days vs. 388 ± 47. days, P = 0.040) in comparison to those testing negative. TelomeScan F35 is a highly sensitive CTC detection system and will be a useful screening tool for early diagnosis of NSCLC patients. Mesenchymal-phenotype CTCs are crucial indicators of chemotherapeutic efficacy in NSCLC patients.