Lee Maria, Kim Eun Jae, Cho Youngnam, Kim Sunshin, Chung Hyun Hoon, Park Noh Hyun, Song Yong-Sang
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Molecular Imaging & Therapy Branch, National Cancer Center, Goyang, Gyeonggi-do, Republic of Korea.
Gynecol Oncol. 2017 May;145(2):361-365. doi: 10.1016/j.ygyno.2017.02.042. Epub 2017 Mar 6.
To test an electrically conductive chip, incorporating a nanoroughened microfluidic platform for the capture of circulating tumor cells (CTCs), and assess its clinical merit in instances of epithelial ovarian cancer (EOC).
A total of 54 patients with EOC recruited between August 2014 and May 2015 were enrolled in this prospective study. CTCs in peripheral blood were detected in advance of primary tumor resection and before initiating adjuvant chemotherapy for recurrent disease. We identified CTCs as EpCAM-positive and DAPI-positive, and CD45-negative feature.
Twenty-four patients with primary disease and 30 patients with recurrences were included in the study. CTCs were detected in 98.1% (53/54). In newly diagnosed patients, median counts of single CTCs and CTC clusters were 4 (0-13) and 1(0-14), respectively. In those with recurrences, median counts were 3 (1-9) and 1(0-24), respectively. Such counts did not differ significantly by tumor stage or by serum CA125 level; but progression-free survival declined at a cutpoint of ≥3 CTCs, and CTC-cluster positivity correlated with platinum resistance. Isolated CTCs (successfully cultured ex vivo in two patients) showed greater sensitivity to anticancer drugs and proliferated more rapidly than did established cell lines.
Proof-of-concept was provided for an electrically conductive and nanoroughened microfluidic platform-based chip designed to capture CTCs in patients with EOC. A larger patient sampling and longer duration of follow-up are needed to determine its suitability for clinical use.
测试一种集成了纳米粗糙化微流控平台以捕获循环肿瘤细胞（CTC）的导电芯片，并评估其在上皮性卵巢癌（EOC）病例中的临床价值。
本前瞻性研究纳入了2014年8月至2015年5月招募的54例EOC患者。在原发性肿瘤切除前和复发性疾病辅助化疗开始前检测外周血中的CTC。我们将CTC鉴定为上皮细胞粘附分子（EpCAM）阳性、4′,6-二脒基-2-苯基吲哚（DAPI）阳性且CD45阴性特征。
研究纳入了24例原发性疾病患者和30例复发患者。54例患者中98.1%（53/54）检测到CTC。新诊断患者中，单个CTC和CTC簇的中位数计数分别为4（0 - 13）和1（0 - 14）。复发患者中，中位数计数分别为3（1 - 9）和1（0 - 24）。这些计数在肿瘤分期或血清CA125水平方面无显著差异；但无进展生存期在CTC≥3个的切点处下降，且CTC簇阳性与铂耐药相关。分离的CTC（两名患者成功在体外培养）比已建立的细胞系对抗癌药物更敏感且增殖更快。
为一种基于导电和纳米粗糙化微流控平台设计用于捕获EOC患者CTC的芯片提供了概念验证。需要更大的患者样本量和更长的随访时间来确定其临床适用性。
