Level of Seven Neuroblastoma-Associated mRNAs Detected by Droplet Digital PCR Is Associated with Tumor Relapse/Regrowth of High-Risk Neuroblastoma Patients
Level of Seven Neuroblastoma-Associated mRNAs Detected by Droplet Digital PCR Is Associated with Tumor Relapse/Regrowth of High-Risk Neuroblastoma Patients
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DOI：
10.1016/j.jmoldx.2019.10.012
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发表时间：
2020-02-01
影响因子：
4.1
通讯作者：
Nishimura, Noriyuki
中科院分区：
文献类型：
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作者：
Thwin, Khin K. M.;Ishida, Toshiaki;Nishimura, Noriyuki
通过实时定量PCR（qPCR）监测几组神经母细胞瘤相关mRNA（NB-mRNA）可用于评估NB患者的微小残留病变。液滴数字PCR（ddPCR）是qPCR的改进，其潜在地提供了两个水平的mRNA的更简单和更可重复的检测。然而，NB患者中的微小残留病是否可以使用一组NB-mRNA通过ddPCR监测尚未测试。在这项研究中，回顾性收集了2011年至2018年期间在两个日本中心进行临床疾病评估的20名高危NB患者的208份骨髓（BM）和67份外周血样本，并通过ddPCR测定了每种NB-mRNA（CRMP 1，DBH，DDC，GAP 43，ISL 1，PHOX 2B和TH mRNA）的水平。水平7 NB-mRNA的表达（定义为各NB-mRNA的联合标记）在BM中高于外周血，但彼此显著相关。根据疾病负担，其随疾病状态（缓解、稳定或进展）和采集时间点（诊断、治疗、治疗后或复发）而变化。在73个治疗后BM样品中，17个复发/再生样品中的浓度显著高于56个非复发/非再生样品。此外，ddPCR在检测相同的73个治疗后BM样品中的7 NB-mRNA方面具有比qPCR更好的预后价值。这项研究表明，ddPCR检测7 NB-mRNA与高风险NB患者的肿瘤复发/再生长显著相关。
Monitoring of several sets of neuroblastoma-associated mRNAs (NB-mRNAs) by real-time quantitative PCR (qPCR) can be used to evaluate minimal residual disease in NB patients. Droplet digital PCR (ddPCR) is an adaption of qPCR that potentially provides simpler and more reproducible detection of tow levels of mRNAs. However, whether minimal residual disease in NB patients can be monitored by ddPCR using a set of NB-mRNAs is not yet tested. In this study, 208 bone marrow (BM) and 67 peripheral blood samples were retrospectively collected from 20 high-risk NB patients with clinical disease evaluation at two Japanese centers between 2011 and 2018, and level of each NB-mRNA (CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs) was determined by ddPCR. Level. of 7NB-mRNAs (defined as the combined signature of each NB-mRNA) was higher in BM than peripheral blood, but correlated significantly with each other. In accordance with disease burden, it varied with disease status (remission, stable, or progression) and collection time point (diagnosis, treatment, post-treatment, or relapse). In 73 post-treatment BM samples, it was significantly higher in 17 relapsed/regrown samples than in 56 non-relapsed/nonregrown samples. Furthermore, ddPCR had a better prognostic value than qPCR in detecting 7NB-mRNAs in the same 73 post-treatment BM samples. This study suggests that ddPCR detection of 7NB-mRNAs is significantly associated with tumor relapse/regrowth in high-risk NB patients.