基于惯性聚焦微流控的循环肿瘤细胞检测技术在脑胶质瘤辅助诊断中的应用研究

刘云默; 潘隆盛; 张宇; 何鹏; 冯世宇

doi:10.12435/j.issn.2095-5227.2024.059

基于惯性聚焦微流控的循环肿瘤细胞检测技术在脑胶质瘤辅助诊断中的应用研究

Application of circulating tumor cell detection technology based on inertial focusing microfluidic in diagnosis of glioma

摘要

摘要:
背景早期诊断和复发监测对脑胶质瘤患者的预后尤为重要，基于惯性聚焦微流控的循环肿瘤细胞检测技术在这一领域具有潜在应用价值。
目的探索惯性聚焦微流控技术对外周血中脑胶质瘤循环肿瘤细胞(circulating tumor cells，CTCs)的捕获能力及其在脑胶质瘤辅助诊断方面的应用价值。
方法选取2022年12月—2023年10月就诊于解放军总医院第一医学中心的脑胶质瘤患者21例，作为病例组；在接受临床干预前，采集患者外周血4 mL，并收集患者临床信息。另选取健康者25例作为对照组，采集外周血4 mL。每份血液标本都通过惯性聚焦微流控芯片技术平台进行CTCs检测。对检测数据和临床情况进行分析。
结果 21例脑胶质瘤患者中，男性9例，女性12例，平均年龄(43.48 ± 14.27)岁；25例健康者中，男性12例，女性13例，平均年龄(44.76 ± 11.38)岁。两组年龄、性别差异无统计学意义。病例组CTCs检出总数M(IQR)：7(3 ~ 19) vs 0(0 ~ 1)，P＜0.001、混合型CTCs M(IQR)：2(0 ~ 16) vs 0(0 ~ 0)，P＜0.001和间质型CTCs M(IQR)：0(0 ~ 5) vs 0(0 ~ 0)，P=0.001检出数均显著高于对照组。ROC曲线分析显示，CTCs检出总数、混合型、间质型CTCs检出个数的ROC曲线下面积(area under curve，AUC)分别为0.987、 0.810、0.702；取病例组CTCs检出计数中位数11为截断值，将病例组研究对象分为高CTCs计数组和低CTCs计数组，两组的血常规结果、炎性指标、WHO分级差异均无统计学意义(P＞0.05)。
结论惯性聚焦微流控技术对于脑胶质瘤患者外周血中的CTCs具有良好的捕获能力，结合免疫组织化学染色，有效排除了炎症细胞对检测结果的影响，提高了检测的准确性。在脑胶质瘤辅助诊断方面具有较高的潜力。

Abstract:
Background Early diagnosis and monitoring of recurrence are particularly important for the prognosis of patients with gliomas.The use of inertial focusing microfluidics-based circulating tumor cell detection technology represents a promising and ideal diagnostic method.
Objective To explore the capture ability of inertial focusing microfluidic technology for circulating tumor cells (CTCs) in peripheral blood of glioma patients and its application value in auxiliary diagnosis of glioma.
Methods A total of 21 glioma patients who visited our hospital from December 2022 to October 2023 were selected as the case group. Before clinical intervention, 4 ml of peripheral blood was collected from each patient, along with gathering their clinical information. Additionally, 25 healthy individuals were chosen as the control group, and 4 ml of peripheral blood was collected from them. Each blood sample underwent CTCs detection using an inertial focusing microfluidic chip technology platform. The detection data and clinical conditions were analyzed.
Results Of the 21 glioma patients, there were 9 males and 12 females, with an average age of (43.48 ± 14.27) years. The control group consisted of 12 males and 13 females with an average age of (44.76 ± 11.38) years. The total number of detected CTCs (MIQR: 7 3-19 vs 0 0-1, P＜0.001), as well as the number of hybrid CTCs (MIQR: 2 0-16 vs 0 0-0, P＜0.001) and mesenchymal CTCs (MIQR: 0 0-5 vs 0 0-0, P=0.001), in the case group were significantly higher than those in the healthy control group. ROC curve analysis revealed that the areas under the curve (AUC) for the total number of detected CTCs, hybrid CTCs, and mesenchymal CTCs were 0.987, 0.810, and 0.702, respectively. Using a median count of 11 as the threshold for detected CTCs in the case group, the subjects were divided into high and low CTC count groups for comparison, showing no statistically significant differences in blood cell results, inflammatory indicators, or WHO grading between the two groups (P＞0.05).
Conclusion Inertial focusing microfluidic technology has excellent capture capabilities for CTCs in the peripheral blood of glioma patients. When combined with immunohistochemistry staining, it enhances the accuracy of detection results, which shows high potential in auxiliary diagnosis of glioma.

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