PO.CL01.16 · 临床研究
循环肿瘤细胞分析用于口腔癌微小残留病灶的早期检测
Circulating tumor cell analysis for early detection of minimal residual disease in oral cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景:在口腔癌(OC)患者中检测微小残留病灶(MRD)的关键临床问题在于缺乏灵敏、标准化的工具来识别治疗后残留但常规影像学或病理学无法检出的残余癌细胞。我们旨在评估循环肿瘤细胞(CTC)能否作为MRD早期检测的生物标志物。
方法:这项纵向观察性研究在基线以及术后1个月、3个月和12个月收集了50例OC患者的血液样本。采用利用惯性微流控原理进行分离的螺旋微流控装置分离CTC。CTC定义为全细胞角蛋白阳性(CK+)或细胞表面波形蛋白阳性(CSV+)、DAPI阳性且CD45阴性。比较了发生复发的患者与保持无病状态患者之间CTC的存在情况。
结果:在1个月时,复发患者的总CTC计数显著更高(均值2.75 vs 0.61;p = 0.0021),且CTC表型阳性率显著升高(细胞角蛋白阳性(CK+)细胞表面波形蛋白阳性(CSV+):p = 0.0001)。在3个月时,CTC差异进一步扩大(均值8.0 vs 0.91;p = 0.0042),多种CTC簇表型呈现强分离,包括CK-CSV+(p = 0.0001)和CK+CSV+(p = 0.0003)。基于CTC的显著差异在1年时持续存在(p = 0.0241)。
结论:CTC作为OC中MRD及即将复发的早期生物标志物展现出强大的应用前景。多种标志物在远早于常规临床检测之前即表现出统计学显著的分离,凸显其早期干预的潜力,支持将其整合到常规临床实践中以改善患者结局。
查看英文原文 English abstract
Background: The key clinical problem in detecting minimal residual disease (MRD) in oral cancer (OC) patients is the lack of sensitive, standardized tools to identify residual cancer cells that remain after treatment but are undetectable by conventional imaging or pathology. We aim to assess whether circulating tumor cells (CTCs) can serve as a biomarker for early detection of MRD.
Methods: This longitudinal observational study collected blood samples from 50 OC patients at baseline, and at one, three, and twelve months following surgery. CTCs were isolated using a spiral microfluidic device that leverages inertial microfluidic principles for separation. CTC was defined as either pan-cytokeratin (CK+) or cell-surface vimentin (CSV+), DAPI positive and CD45 negative. The presence of CTCs was compared between patients who experienced recurrence and those who remained disease-free.
Results: At one month, patients with recurrence showed significantly higher total CTC counts (mean 2.75 vs 0.61; p = 0.0021) and significantly elevated CTC phenotype positivity (cytokeratin positive (CK+) cell surface vimentin positive (CSV+): p = 0.0001). At three months, CTC differences further widened (mean 8.0 vs 0.91; p = 0.0042), with strong separation across multiple CTC cluster phenotypes, including CK-CSV+ (p = 0.0001) and CK+CSV+ (p = 0.0003). Significant CTC-based differences persisted at one year (p = 0.0241).
Conclusions: CTCs demonstrate strong promise as early biomarkers for MRD and impending recurrence in OC. Multiple markers exhibit statistically significant separation well in advance of conventional clinical detection, highlighting their potential for early intervention, supporting its integration into routine clinical practice for improved patient outcomes.
利益披露 Disclosure
X. Zhang, None..
S. Vasani, None..
W. A. Afridi, None..
D. A. Ferreira, None..
O. Breik, None..
G. Hartel, None..
L. Kenny, None..
C. Punyadeera, None.