A novel approach using telomerase-specific replication-selective adenovirus for detection of circulating tumor cells in breast cancer patients
A novel approach using telomerase-specific replication-selective adenovirus for detection of circulating tumor cells in breast cancer patients
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DOI：
10.1007/s10549-011-1603-2
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发表时间：
2011-08-01
影响因子：
3.8
通讯作者：
Noguchi, Shinzaburo
中科院分区：
文献类型：
--
作者：
Kim, Seung Jin;Masago, Akinori;Noguchi, Shinzaburo
本研究的目的是建立一种新的方法来检测循环肿瘤细胞（CTC）在乳腺癌患者的端粒酶特异性复制选择性腺病毒OBP-401。一旦转染，OBP-401只能在表达端粒酶的细胞中复制，并在复制时发射荧光，使得转染的细胞变得容易识别。从50名转移性乳腺癌患者和27名早期乳腺癌患者中抽取外周血样本。对血液样品进行OBP-401和CellSearch测定以检测CTC，并比较结果。OBP-401测定的回收率为7.5 ml血液中的1个CTC，并且具有高特异性，因为在80名健康对照中未观察到CTC。在50例转移性患者中，21例患者（42%）被确定为OBP-401检测阳性，27例患者（54%）被确定为CellSearch检测阳性。CellSearch检测显示激素受体（HR）阳性肿瘤的阳性率显著较高（雌激素受体和/或孕激素受体阳性肿瘤）（61%，25/41，P = 0.012）或CA 15 -3阳性肿瘤（69%，24/35，P = 0.003）分别高于HR阴性肿瘤（13%，1/8）或CA 15 -3阴性肿瘤（21%，3/14）。相反，无论HR状态（阳性：44% vs.阴性：38%，P = 0.738）或CA 15 -3阳性（阳性：40% vs.阴性：50%，P = 0.523）如何，OBP-401测定结果均相似。在27名早期患者中，分别通过OBP-401测定和CellSearch测定鉴定了4名患者（15%），但CTC阳性患者中没有重叠。总之，在转移性和早期乳腺癌患者中，OBP-401测定在CTC的检测率方面与CellSearch测定相当。然而，两种测定法在CTC患者中存在很大差异。OBP-401测定可分离具有CellSearch测定所检测的CTC不具有的其他生物学特征的CTC。
The aim of this study was to develop a new method for detecting circulating tumor cells (CTCs) in breast cancer patients by using the telomerase-specific replication-selective adenovirus OBP-401. Once transfected, OBP-401 can replicate only in telomerase expressing cells and emit fluorescence as it replicates so that the transfected cells become easily recognizable. Peripheral blood samples were drawn from 50 metastatic breast cancer patients and 27 early breast cancer patients. Blood samples were subjected to both the OBP-401 and CellSearch assays for the detection of CTCs and the results were compared. The recovery rate of the OBP-401 assay was one CTC in 7.5 ml blood combined with high specificity since no CTC was observed in 80 healthy controls. In 50 metastatic patients, 21 patients (42%) were identified as positive with the OBP-401 assay and 27 patients (54%) with the CellSearch assay. The CellSearch assay showed a significantly higher positivity for hormone receptor (HR)-positive tumors (estrogen receptor and/or progesterone receptor-positive tumors) (61%, 25/41, P = 0.012) or CA15-3-positive tumors (69%, 24/35, P = 0.003) than for HR-negative tumors (13%, 1/8) or CA15-3-negative tumors (21%, 3/14), respectively. Contrary, the OBP-401 assay results were similar regardless of their HR status (positive: 44% vs. negative: 38%, P = 0.738) or CA15-3 positivity (positive: 40% vs. negative: 50%, P = 0.523). Of the 27 early stage patients, four patients (15%) were identified by the OBP-401 assay and by the CellSearch assay, respectively, but there was no overlap in the CTCs-positive patients. In conclusion, the OBP-401 assay is comparable to the CellSearch assay in the detection rate of CTCs in both metastatic and early breast cancer patients. However, there was a great discrepancy in patients with CTCs between both assays. The OBP-401 assay may isolate CTCs with other biological characteristics which CTCs detected by the CellSearch assay do not have.