Wang Hye-Young, Ahn Sungwoo, Kim Sunghyun, Park Sunyoung, Jung Dongju, Park Sangjung, Han Hyunju, Sohn JooHyuk, Kim SeungIl, Lee Hyeyoung
M&D, Inc., Wonju Eco Environmental Technology Center, Wonju, Gangwon, Republic of Korea.
Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, 1 Yonseidae-gil, Wonju, Gangwon, 220-710, Republic of Korea.
Int J Clin Oncol. 2015 Oct;20(5):878-90. doi: 10.1007/s10147-015-0798-3. Epub 2015 Feb 24.
Breast cancer is a highly prevalent disease among women worldwide. While the expression of certain proteins within breast cancer tumors is used to determine the prognosis and select therapies, additional markers need to be identified. Circulating tumor cells (CTCs) are constituent cells that have detached from a primary tumor to circulate in the bloodstream. CTCs are considered the main source of breast cancer metastases; therefore, detection of CTCs could be a promising diagnostic method for metastatic breast cancer.
In this study, the CircleGen CTC RT-qDx assay was used to analyze the mRNA expression levels of six CTC-specific markers including EpCAM, CK19, HER2, Ki67, hTERT, and vimentin with a total of 692 peripheral whole blood samples from 221 breast cancer patients and 376 healthy individuals.
This assay showed high specificity with multiple markers; none of the healthy controls were detected positive, whereas 21.7 and 14 % of breast cancer patients were positive for EpCAM and CK19, respectively. Of the 221 breast cancer patients, 84 (38 %), 46 (20.8 %), 83 (37.6 %), and 39 (17.6 %) were positively for HER2, Ki67, hTERT, and vimentin mRNA, respectively. Of the 84 patients who were HER2 positive, nine (4 %) were also positive for EpCAM, CK19, Ki67, hTERT, and vimentin. Of the 139 breast cancer patients who were HER2 negative, 65 (29.1 %) were negative for EpCAM, CK19, Ki67, hTERT, and vimentin. Furthermore, the EpCAM-positive population decreased from 21.5 to 8.3 % after completion of anti-tumor treatment (TP4). Similarly, the CK19, HER2, hTERT, and vimentin positives also decreased from 13.9 to 9.5 %, from 37.7 to 21.4 %, from 37.2 to 33.3 %, and from 17.5 to 14.3 %, respectively, after completion of anti-tumor treatment. In contrast, the Ki67 positives increased from 20.6 to 41.7 % after completion of anti-tumor treatment.
mRNA overexpression of six CTC-specific markers was detected by the CircleGen CTC RT-qDx assay with high specificity, and the obtained mRNA expression levels of CTC-specific markers might provide useful criteria to select appropriate anti-tumor treatment for breast cancer patients.
乳腺癌是全球女性中一种高度流行的疾病。虽然乳腺癌肿瘤内某些蛋白质的表达用于确定预后和选择治疗方法，但仍需要鉴定其他标志物。循环肿瘤细胞（CTC）是从原发性肿瘤脱离并在血液中循环的组成细胞。CTC被认为是乳腺癌转移的主要来源；因此，检测CTC可能是转移性乳腺癌一种有前景的诊断方法。
在本研究中，使用CircleGen CTC RT-qDx检测法分析了六种CTC特异性标志物（包括EpCAM、CK19、HER2、Ki67、hTERT和波形蛋白）的mRNA表达水平，共检测了来自221例乳腺癌患者和376例健康个体的692份外周全血样本。
该检测法对多种标志物显示出高特异性；健康对照均未检测出阳性，而分别有21.7%和14%的乳腺癌患者EpCAM和CK19呈阳性。在221例乳腺癌患者中，HER2、Ki67、hTERT和波形蛋白mRNA阳性的分别有84例（38%）、46例（20.8%）、83例（37.6%）和39例（17.6%）。在84例HER2阳性患者中，9例（4%）同时EpCAM、CK19、Ki67、hTERT和波形蛋白也呈阳性。在139例HER2阴性的乳腺癌患者中，65例（29.1%）EpCAM、CK19、Ki67、hTERT和波形蛋白均为阴性。此外，抗肿瘤治疗完成后（TP4），EpCAM阳性人群从21.5%降至8.3%。同样，抗肿瘤治疗完成后，CK19、HER2、hTERT和波形蛋白阳性率也分别从13.9%降至9.5%、从37.7%降至21.4%、从37.2%降至33.3%、从17.5%降至14.3%。相反，抗肿瘤治疗完成后Ki67阳性率从20.6%升至41.7%。
通过CircleGen CTC RT-qDx检测法检测到六种CTC特异性标志物的mRNA过表达具有高特异性，并且获得的CTC特异性标志物的mRNA表达水平可能为为乳腺癌患者选择合适的抗肿瘤治疗提供有用的标准。
