染色体核型分析的循环肿瘤细胞作为一种新型生物标志物用于鼻咽癌的诊断和治疗。
Circulating tumor cells with karyotyping as a novel biomarker for diagnosis and treatment of nasopharyngeal carcinoma.
机构信息
Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, 37 GuoXueXiang, Wuhou District, Chengdu, 610041, Sichuan, China.
Cytelligen, San Diego, California, USA.
出版信息
BMC Cancer. 2018 Nov 19;18(1):1133. doi: 10.1186/s12885-018-5034-x.
BACKGROUND
Circulating tumor cells (CTCs) have been considered great clinical significance in various cancers. However, it remains unknown that how is the role of CTCs in patients with nasopharyngeal carcinoma (NPC). We investigated the value of CTCs enumeration and karyotyping in NPC.
METHODS
In the present study, we applied integrated subtraction enrichment and immunostaining-fluorescence in situ hybridization (SE-iFISH) automatic testing system to detect and characterize CTCs of NPC patients. Enumeration and aneuploidy of chromosome 8 in CTCs were examined in various stages of patients with NPC. The changes of CTCs number and karyotyping post to chemotherapy were investigated in NPC.
RESULTS
CTCs were detected by SE-iFISH in 46 out of 50 pre-treatment NPC patients, and performed a positive rate of 92.0%. No significant association was found between disease staging and CTCs detection rate. CTCs number constantly increased with TNM stage rising (from stage II to stage IV) no matter in newly diagnosed patients without distant metastasis (M0) and relapsed or distant metastatic patients. The number of CTCs decreased after treatment in patients with partial response (PR), while increased in patients with progressive disease or stable disease (PD/SD). More interestingly, CTCs karyotyping indicated that aneuploidy of chromosome 8 in CTCs was dramatically related to chemotherapeutic efficacy in NPC. Positive correlation was found between CTCs count and plasma EBV DNA level of NPC patients.
CONCLUSIONS
CTCs could be detected in various stages of NPC patients using SE-iFISH. CTCs number could indicate the severity degree of disease in NPC. Dynamically monitoring the variations in CTCs number may predict chemotherapy efficacy during treatment. CTCs karyotyping is related to the sensibility of chemotherapy and drug resistance, and karyotyping of CTCs might predict therapeutic efficacy and evaluate chemo-resistance in NPC. CTCs could be used as a monitoring indicator in the fields of treatment, diagnosis and follow-up of NPC.
背景
循环肿瘤细胞（CTCs）在各种癌症中具有重要的临床意义。然而，目前尚不清楚 CTCs 在鼻咽癌（NPC）患者中的作用。本研究旨在探讨 CTCs 计数和核型分析在 NPC 中的价值。
方法
本研究采用整合性消减富集和免疫荧光原位杂交（SE-iFISH）自动检测系统，检测和分析 NPC 患者的 CTCs。检测 NPC 患者不同分期 CTC 计数和 8 号染色体非整倍体。分析 NPC 患者化疗后 CTC 数量和核型变化。
结果
SE-iFISH 检测到 50 例初治 NPC 患者中的 46 例（92.0%）存在 CTCs。疾病分期与 CTCs 检出率之间无显著相关性。无论是否存在远处转移（M0），CTC 数量均随 TNM 分期升高而持续增加（从 II 期到 IV 期）。部分缓解（PR）患者治疗后 CTC 数量减少，而疾病进展或稳定（PD/SD）患者则增加。更有趣的是，CTC 核型分析表明，8 号染色体非整倍体与 NPC 化疗疗效显著相关。NPC 患者 CTC 计数与血浆 EBV DNA 水平呈正相关。
结论
SE-iFISH 可检测 NPC 患者的 CTCs。CTC 数量可反映 NPC 患者的疾病严重程度。动态监测 CTCs 数量的变化可能有助于预测治疗期间的化疗疗效。CTC 核型与化疗敏感性和耐药性相关，CTC 核型分析可能有助于预测 NPC 的治疗疗效和评估化疗耐药性。CTC 可作为 NPC 治疗、诊断和随访的监测指标。
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