Second Department of Surgery, University of Occupational and Environmental Health, Kitakyushu, Japan.
Central Research Laboratories, Toyama Industrial Technology Center, Takaoka, Japan.
Cancer Sci. 2022 Mar;113(3):1028-1037. doi: 10.1111/cas.15255. Epub 2022 Jan 28.
Detecting rare circulating tumor cells (CTCs) in the bloodstream is extremely challenging. We had previously developed a novel polymeric microfluidic device, "CTC-chip," for capturing CTCs and have shown high capture efficiency in lung cancer cell lines by conjugating Abs against epithelial cell adhesion molecules (EpCAM). This study aimed to optimize the EpCAM-chip and clarify the prognostic impact of CTCs in lung cancer patients. Of 123 patients with pathologically proven lung cancer, both progression-free survival (P = .037) and cancer-specific survival (P = .0041) were predominantly poor when CTCs were detected before treatment. After classification into surgical and chemotherapy groups, progression-free survival was worse in CTC-positive patients in both groups (surgery, P = .115; chemotherapy, P = .012), indicating that the detection of baseline CTCs is a risk factor for recurrence and progression. Furthermore, we recovered captured CTCs using micromanipulators and undertook mutation analysis using PCR. Thus, the EpCAM-chip is a highly sensitive system for detecting CTCs that contributes to the prediction of recurrence and progression and enables genetic analysis of captured CTCs, which could open new diagnostic, therapeutic, and prognostic options for lung cancer patients.
检测血液中罕见的循环肿瘤细胞 (CTCs) 极具挑战性。我们之前开发了一种新型的聚合物微流控设备“CTC-chip”，用于捕获 CTC，并通过连接针对上皮细胞黏附分子 (EpCAM) 的抗体显示出在肺癌细胞系中高的捕获效率。本研究旨在优化 EpCAM-chip，并阐明 CTC 在肺癌患者中的预后影响。在 123 名经病理证实的肺癌患者中，在治疗前检测到 CTC 时，无进展生存期 (P =.037) 和癌症特异性生存期 (P =.0041) 主要较差。在分为手术和化疗组后，CTC 阳性患者在两组中的无进展生存期均较差（手术，P =.115；化疗，P =.012），表明基线 CTC 的检测是复发和进展的危险因素。此外，我们使用微操纵器回收捕获的 CTC，并使用 PCR 进行突变分析。因此，EpCAM-chip 是一种用于检测 CTC 的高灵敏度系统，有助于预测复发和进展，并能够对捕获的 CTC 进行基因分析，这可能为肺癌患者提供新的诊断、治疗和预后选择。
