单中心神经母细胞瘤标志物检测在儿童神经母细胞瘤中的应用及分析

尹泽西, 田鑫, 李湘, 汤文芳, 刘丹宁, 贺湘玲

中国当代儿科杂志 ›› 2026, Vol. 28 ›› Issue (9) : 1113-1119.

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中国当代儿科杂志 ›› 2026, Vol. 28 ›› Issue (9) : 1113-1119. DOI: 10.7499/j.issn.1008-8830.2512035
论著·临床研究

单中心神经母细胞瘤标志物检测在儿童神经母细胞瘤中的应用及分析

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Single-center application and analysis of neuroblastoma marker detection in childhood neuroblastoma

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摘要

目的 探讨骨髓(bone marrow, BM)及外周血(peripheral blood, PB)中5种神经母细胞瘤(neuroblastoma, NB)标志物(嗜铬粒蛋白A、双皮质素、多巴脱羧酶、配对样同源框2b及酪氨酸羟化酶,合称NB5)的mRNA表达对儿童NB的转移、复发的预测价值,对比流式细胞术微小残留病(measurable residual disease, MRD)检测效能,并分析其与无进展生存(progression‑free survival, PFS)期的相关性。 方法 回顾性收集2018年10月—2024年12月湖南省人民医院47例NB患儿的临床资料,采用实时荧光定量逆转录酶聚合酶链反应检测BM及PB中NB5表达。采用Kaplan‑Meier法进行生存分析,采用多因素Cox回归校正混杂因素。 结果 共纳入47例患儿,其中高危患儿44例(94%),低危患儿3例(6%)。共完成99例次BM检测,BM‑NB5阳性率为31%(31/99),显著高于MRD阳性率(19%,19/99)及BM形态学阳性率(15%,15/99)(均P<0.001)。19例配对BM‑PB样本中,PB‑NB5阳性4例,BM‑NB5阳性8例,阳性一致率为100%,阴性一致率为47%,Kappa值为0.321(弱一致性)。log‑rank分析显示,MRD阴性患儿中NB5阳性组PFS率显著短于阴性组(P=0.040)。Cox分析显示,NB5表达与PFS率呈临界相关(风险比为4.367,95%CI:0.896~21.277,P=0.068)。 结论 BM‑NB5检测对高危NB患儿MRD的检出灵敏度优于流式MRD及BM形态学,可早期预警复发风险。NB5表达对NB患儿的预后可能存在分层趋势,需扩大样本量进一步验证其独立预后价值。

Abstract

Objective To investigate the predictive value of mRNA expression of five neuroblastoma (NB) markers—chromogranin A, doublecortin, dopa decarboxylase, paired-like homeobox 2b, and tyrosine hydroxylase (collectively referred to as NB5)—in bone marrow (BM) and peripheral blood (PB) for metastasis and recurrence in pediatric NB, to compare its performance with conventional flow cytometric measurable residual disease (MRD) detection, and to analyze its correlation with progression-free survival (PFS). Methods Clinical data of 47 children with NB admitted to Hunan Provincial People's Hospital from October 2018 to December 2024 were retrospectively collected. Real-time quantitative reverse transcription-polymerase chain reaction was used to detect NB5 expression in BM and PB. Survival was analyzed by the Kaplan-Meier method, and multivariable Cox regression was performed to adjust for confounders. Results A total of 47 children were enrolled, including 44 high-risk (94%) and 3 low-risk (6%) patients. Overall, 99 BM tests were completed. The BM-NB5 positivity rate was 31% (31/99), significantly higher than the MRD positivity rate (19%, 19/99) and the BM morphologic positivity rate (15%, 15/99) (both P<0.001). Among 19 paired BM-PB samples, PB-NB5 was positive in 4 cases and BM-NB5 was positive in 8 cases; the positive concordance rate was 100%, the negative concordance rate was 47%, and the kappa coefficient was 0.321 (weak agreement). Log-rank analysis showed that among MRD-negative patients, the NB5-positive group had significantly shorter PFS than the NB5-negative group (P=0.040). Cox regression indicated a marginal association between NB5 expression and PFS (HR=4.367, 95%CI: 0.896-21.277, P=0.068). Conclusions BM-NB5 detection shows superior sensitivity for MRD identification compared with flow cytometric MRD and BM morphology in high-risk NB patients and can provide early warning of recurrence risk. NB5 expression appears to stratify prognosis in NB, warranting validation in a larger cohort to confirm its independent prognostic value.

关键词

神经母细胞瘤 / NB5检测 / 实时荧光定量逆转录酶聚合酶链反应 / 儿童

Key words

Neuroblastoma / NB5 detection / Real-time quantitative reverse transcription polymerase chain reaction / Child

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尹泽西, 田鑫, 李湘, . 单中心神经母细胞瘤标志物检测在儿童神经母细胞瘤中的应用及分析[J]. 中国当代儿科杂志. 2026, 28(9): 1113-1119 https://doi.org/10.7499/j.issn.1008-8830.2512035
Ze-Xi YIN, Xin TIAN, Xiang LI, et al. Single-center application and analysis of neuroblastoma marker detection in childhood neuroblastoma[J]. Chinese Journal of Contemporary Pediatrics. 2026, 28(9): 1113-1119 https://doi.org/10.7499/j.issn.1008-8830.2512035

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作者均声明无利益冲突。

基金

湖南省科技创新计划项目(2024JJ9153)

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