Identification of a Five-Gene Signature Derived From MYCN Amplification and Establishment of a Nomogram for Predicting the Prognosis of Neuroblastoma.

Identification of a Five-Gene Signature Derived From MYCN Amplification and Establishment of a Nomogram for Predicting the Prognosis of Neuroblastoma.
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MYCN 扩增衍生的五基因特征的鉴定以及用于预测神经母细胞瘤预后的诺模图的建立

DOI:
10.3389/fmolb.2021.769661
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发表时间:
2021
影响因子:
5
通讯作者:
Zhao Q
Zhao Q
中科院分区:
生物学3区
文献类型:
--
作者:
Xia Y;Li X;Tian X;Zhao Q

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背景:神经母细胞瘤(Neuroblastoma, NB)是儿童最常见的实体肿瘤,表现出不同的基因组异常和临床行为。虽然临床表现与遗传异常关系的研究取得了重大进展,但如何预测患者的预后以促进个性化治疗仍然是一个重大挑战。材料与方法:从gene expression Omnibus (GEO)数据库、ArrayExpress数据库和therapeutic applied Research to Generate Effective therapies (TARGET)数据库中下载6组基因表达数据集及相关临床数据。根据有无MYCN扩增将患者分为两组。在两组间鉴定差异表达基因(DEGs)。对这些deg进行富集分析,进一步探讨NB的分子机制。采用逐步Cox回归分析建立五基因预后特征,并通过外部验证进一步评估其预测性能。多因素Cox回归分析探讨NB的独立预后因素。利用算法对免疫相关性进行了评价,并构建了图。结果:建立了由CPLX3、GDPD5、SPAG6、NXPH1和AHI1组成的5个基因特征。五基因标记在预测生存方面表现良好,并被证明优于国际神经母细胞瘤分期系统(INSS)分期和MYCN扩增状态。最后建立了基于五基因标记的nomogram,并对其临床疗效进行了验证。结论:总的来说,我们的研究开发了一个新的五基因标记,并成功建立了一个准确预测NB患者生存的预后nomogram。本文的研究结果有助于将患者分为亚组,并确定最佳的个体化治疗方案。
Background: Neuroblastoma (NB), the most common solid tumor in children, exhibits vastly different genomic abnormalities and clinical behaviors. While significant progress has been made on the research of relations between clinical manifestations and genetic abnormalities, it remains a major challenge to predict the prognosis of patients to facilitate personalized treatments. Materials and Methods: Six data sets of gene expression and related clinical data were downloaded from the Gene Expression Omnibus (GEO) database, ArrayExpress database, and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. According to the presence or absence of MYCN amplification, patients were divided into two groups. Differentially expressed genes (DEGs) were identified between the two groups. Enrichment analyses of these DEGs were performed to dig further into the molecular mechanism of NB. Stepwise Cox regression analyses were used to establish a five-gene prognostic signature whose predictive performance was further evaluated by external validation. Multivariate Cox regression analyses were used to explore independent prognostic factors for NB. The relevance of immunity was evaluated by using algorithms, and a nomogram was constructed. Results: A five-gene signature comprising CPLX3, GDPD5, SPAG6, NXPH1, and AHI1 was established. The five-gene signature had good performance in predicting survival and was demonstrated to be superior to International Neuroblastoma Staging System (INSS) staging and the MYCN amplification status. Finally, a nomogram based on the five-gene signature was established, and its clinical efficacy was demonstrated. Conclusion: Collectively, our study developed a novel five-gene signature and successfully built a prognostic nomogram that accurately predicted survival in NB. The findings presented here could help to stratify patients into subgroups and determine the optimal individualized therapy.
DOI: 10.1093/jnci/djt006
发表时间: 2013-03-20
期刊: Journal of the National Cancer Institute
影响因子: --
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Chen M;Gallipoli P;DeGeer D;Sloma I;Forrest DL;Chan M;Lai D;Jorgensen H;Ringrose A;Wang HM;Lambie K;Nakamoto H;Saw KM;Turhan A;Arlinghaus R;Paul J;Stobo J;Barnett MJ;Eaves A;Eaves CJ;Holyoake TL;Jiang X
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DOI: 10.1101/cshperspect.a014415
发表时间: 2013-10-01
影响因子: 5.4
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DOI: 10.1172/jci67428
发表时间: 2013-07-01
影响因子: 15.9
作者:
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DOI: 10.1096/fj.12-209502
发表时间: 2012-12-01
期刊: FASEB JOURNAL
影响因子: 4.8
作者:
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通讯作者: Gerhauser, Clarissa