MYCN RNA levels determined by quantitative in situ hybridization is better than MYCN gene dosages in predicting the prognosis of neuroblastoma patients
MYCN RNA levels determined by quantitative in situ hybridization is better than MYCN gene dosages in predicting the prognosis of neuroblastoma patients
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DOI：
10.1038/s41379-019-0410-x
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发表时间：
2020-04-01
期刊：
影响因子：
7.5
通讯作者：
Jeng, Yung-Ming
中科院分区：
文献类型：
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作者：
Chang, Hsiu-Hao;Tseng, Yu-Fen;Jeng, Yung-Ming
本研究旨在探讨定量RNA原位杂交检测神经母细胞瘤中MYCN RNA表达对预后的影响及其与MYCN扩增的关系。应用超灵敏的RNAScope定量RNA原位杂交技术检测了69例神经母细胞瘤组织中MYCN RNA的表达。分析MYCN RNA表达、MYCN扩增与神经母细胞瘤其他临床病理变量的相关性。在69例神经母细胞瘤中，有30例(43%)检测到MYCN RNA高表达，主要发生在未分化或低分化的组织中。MYCN RNA的高表达与MYCN扩增(P<；0.001)和其他不良预后因素显著相关，包括确诊时年龄较大(P<；18个月，P=0.017)、临床晚期(国际神经母细胞瘤分期系统3、4期，P=0.002)、国际神经母细胞瘤病理分类肿瘤组织学不良(P<；0.001)和高危儿童肿瘤组风险组(P=0.001)。在Kaplan-Meier分析中，定量原位杂交法测定的MYCN RNA水平在区分神经母细胞瘤患者预后良好和不良组方面优于显色原位杂交法测定的MYCN基因剂量。在多因素分析中，我们进一步证实MYCN RNA的高表达是无事件和总体生存的一个独立的不良预后因素。此外，MYCN RNA的高表达预示着具有MYCN非扩增或高危儿童肿瘤组风险组的神经母细胞瘤患者的不良生存结局。综上所述，本研究首次报道了MYCN RNA原位杂交在神经母细胞瘤中的应用，并证实MYCN RNA的高表达可能是一个比MYCN扩增更好的预测神经母细胞瘤患者预后的生物标志物。
The aim of this study was to investigate the prognostic role of MYCN RNA expression by quantitative RNA in situ hybridization and its association with MYCN amplification in neuroblastoma. MYCN RNA expression in 69 neuroblastoma tumors was evaluated by an ultrasensitive quantitative RNA in situ hybridization technique, RNAscope. The correlations between MYCN RNA expression, MYCN amplification, and other clinicopathologic variables of neuroblastoma were analyzed. High expression levels of MYCN RNA were detected 30 of 69 (43%) of neuroblastomas, mainly in those with undifferentiated or poorly differentiated histology. High expression of MYCN RNA was significantly associated with MYCN amplification (P < 0.001) and other adversely prognostic factors, including older age at diagnosis (>18 months, P = 0.017), advanced clinical stage (International Neuroblastoma Staging System stage 3, 4, P = 0.002), unfavorable International Neuroblastoma Pathology Classification tumor histology (P < 0.001), and high-risk Children's Oncology Group risk group (P = 0.001). In Kaplan-Meier analysis, MYCN RNA levels determined by quantitative in situ hybridization were better than MYCN gene dosages determined by chromogenic in situ hybridization in discriminating good and poor prognostic groups of neuroblastoma patients. In multivariate analysis, we further confirmed that high expression of MYCN RNA was an independent adverse prognostic factor for event-free and overall survival. Furthermore, high expression of MYCN RNA predicted unfavorable survival outcomes for neuroblastoma patients with MYCN non-amplification or high-risk Children's Oncology Group risk group. In conclusion, our study is the first report to show the application of MYCN RNA in situ hybridization in neuroblastoma and established that high expression of MYCN RNA could be a better biomarker than MYCN amplification for predicting poor prognosis of neuroblastoma patients.