Deng Xiaobin,Peng Liang,Zhao Zhenzhen,et al.Clinical application of circulating tumor cells in the diagnosis and prognosis of neuroblastoma[J].Journal of Clinical Pediatric Surgery,2023,22(08):741-746.[doi:10.3760/cma.j.cn101785-202301021-008]
循环肿瘤细胞在神经母细胞瘤临床诊断及预后评估中的应用研究
- Title:
- Clinical application of circulating tumor cells in the diagnosis and prognosis of neuroblastoma
- Keywords:
- Circulating Tumor Cells; Neuroblastoma; Diagnosis; Prognosis
- 摘要:
- 目的 研究循环肿瘤细胞（circulating tumor cells，CTCs）与神经母细胞瘤（neuroblastoma，NB）临床及病理特征的相关性，探讨CTCs检测在NB诊疗中的应用价值。方法 本研究为回顾性研究。选取2021年1月至2022年9月重庆医科大学附属儿童医院肿瘤外科收治的87例经病理检查确诊的NB患儿作为研究对象，并将其设为病例组，收集患儿年龄、性别、肿瘤分期、转移、生存情况等临床资料，以及尿香草扁桃酸（vanillyl mandelic acid，VMA）水平、CTCs检测结果等。选取20名健康儿童作为对照组。两组均采用乙二胺四乙酸（ethylenediaminetetraacetic acid，EDTA）抗凝的真空采血管采集静脉血6 mL，采用CytoSorter? CTCs检测系统，通过细胞表面波形蛋白（cell surface vimentin，CSV）抗体纳米微流控芯片免疫捕获CTCs，采用anti-CSV Ab和anti-GD2 Ab鉴定肿瘤细胞。使用SPSS 26.0和Graphpad Prism 9进行数据处理和图表制作。结果 CTCs阳性率病例组为67.8%（59/87），对照组为5%（1/20），差异有统计学意义（P<0.01）。CTCs阳性率与年龄、肿瘤大小、国际神经母细胞瘤危险度分级协作组（International Neuroblastoma Risk Group，INRG）分期及危险度分层、骨髓转移、骨转移、生存状态、VMA水平相关（P<0.05）；与性别、肿瘤类型、Shimada分型、淋巴结转移、Mycn扩增与否无关（P>0.05）。CTCs的检出数量在年龄 ≥ 18个月、Shimada分型为预后不良型，肿瘤长泾大于5 cm、伴有骨/骨髓转移、更高INRG分期及危险度分层的患儿中明显升高，差异有统计学意义（P<0.05）。CTCs检出数量与生存状态明显相关，存活患儿CTCs检出数量明显低于死亡患儿，差异有统计学意义（P=0.002）。本组87例NB患儿最长随访时间2.5年，总体生存率为53.9%（62/87），CTCs阳性患儿生存率明显低于CTCs阴性患儿（46.8%比87.1%），差异有统计学意义（P=0.001）。相比24 h尿VMA，CTCs检出率对于NB有更高的诊断效能（P=0.009）。结论 CTCs在NB患儿中有较高检出率，其阳性率与临床不良预后结局相关。CTCs可以作为判断NB预后的一个指标。
- Abstract:
- Objective To elucidate the relationship between circulating tumor cells (CTCs) and clinicopathological characteristics of neuroblastoma (NB) and explore the clinical application value of CTCs detection in the diagnosis and treatment of NB.Methods A total of 87 children with pathologically diagnosed NB from January 2021 to September 2022 were selected as study group.Clinical data, laboratory tests and CTCs test results were recorded.At the same time, 20 healthy children were selected as negative controls.A total of 6 mL of venous anticoagulant blood from each subject was collected and CTCs were enriched by specific antibody nanofluidic chip immunoassay with CytoSorter? CTCs sorting system and identified by anti-CSV Ab and anti-GD2 Ab.SPSS26.0 software and Graphpad Prism 9 were employed for data processing and graphing.Results CTCs were detected in 67.8% NB children and in 5% healthy controls.Significant differences existed between two groups (P<0.01).CTCs positive rate was correlated with age, tumor size, International Neuroblastoma Risk Group (INRG) stage, risk stratification, bone/bone marrow metastasis, survival status and 24 h VMA level, yet not with gender, tumor type, Shimada classification, lymph node metastasis or Mycn amplification.CTCs number was higher in children aged above 18 months, uFH classification, tumor size >5 cm and with bone/bone marrow metastases.The number of CTCs was higher in more advanced stage and higher risk stratification children as well as in deceased individuals.The longest follow-up time in this group was 2.5 years, the overall survival rate of this study was 53.9% and the survival rate of CTCs-positive children was significantly lower than that of CTCs-negative counterparts (46.8% vs.87.1%, P=0.002).Taking CTCs as a diagnostic criteria of NB, the efficacy was higher than that of urinary VMA.Conclusion CTCs have a high detection rate in NB children and its positive rate is correlated with unfavorable clinical prognostic factors.And CTCs may be used as an indicator for evaluating the prognosis of NB.
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备注/Memo
收稿日期:2023-01-29。
基金项目:重庆市科卫联合医学科研项目（2021MSXM073）
通讯作者:杨超,Email:400843@hospital.cqmu.edu.cn