TP53 和与 TP53 相关的基因与小儿神经母细胞瘤的预后相关。
TP53 and TP53-associated genes are correlated with the prognosis of paediatric neuroblastoma.
机构信息
Medical Research Center, Fujian Maternity and Child Health Hospital, Fuzhou, Fujian, China.
State Key Laboratory for Medical Genomics, Shanghai Institute of Hematology, Rui-Jin Hospital Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
出版信息
BMC Genom Data. 2022 Jun 2;23(1):41. doi: 10.1186/s12863-022-01059-5.
BACKGROUND
TP53 is rarely mutated in paediatric neuroblastoma. The prognosis of TP53 and TP53-associated genes in paediatric neuroblastoma is unclear. The objectives of the study were to analyse datasets of 2477 paediatric neuroblastoma patients from eight independent cohorts to reveal the prognosis of TP53 and TP53-associated genes.
RESULTS
High TP53 mRNA expression was associated with shortened event-free survival and overall survival in paediatric neuroblastoma. Moreover, a higher enrichment score of the TP53 signalling pathway was associated with worse clinical outcomes of paediatric neuroblastoma. Among the genes associated with TP53, CCNE1, CDK2 and CHEK2 were correlated with unfavourable clinical outcomes, while SESN1 was correlated with favourable clinical outcomes of paediatric neuroblastoma in the eight independent neuroblastoma cohorts. TP53, CCNE1, CDK2 and CHEK2 were overexpressed in neuroblastoma patients with MYCN amplification, while SESN1 was downregulated in neuroblastoma patients with MYCN amplification. CCNE1, SESN1, MYCN amplification and age at diagnosis were independent prognostic markers of neuroblastoma. CCNE1 was also highly expressed in paediatric neuroblastoma patients with an age at diagnosis ≥ 18 months, while SESN1 was downregulated in paediatric neuroblastoma patients with an age at diagnosis ≥ 18 months. Combinations of CCNE1 with age at diagnosis or combinations of SESN1 with age at diagnosis achieved superior prognostic effects in paediatric neuroblastoma. Finally, we constructed a nomogram risk model of paediatric neuroblastoma based on age and TP53, CCNE1, CDK2, CHEK2 and SESN1 expression. The nomogram model could predict the overall survival of paediatric neuroblastoma and MYCN nonamplified paediatric neuroblastoma with high specificity and sensitivity.
CONCLUSIONS
TP53 and TP53-associated genes CCNE1, CDK2, CHEK2 and SESN1 were significantly associated with the clinical outcomes of paediatric neuroblastoma.
背景
TP53 在小儿神经母细胞瘤中很少发生突变。TP53 和与 TP53 相关的基因在小儿神经母细胞瘤中的预后尚不清楚。本研究的目的是分析来自 8 个独立队列的 2477 例小儿神经母细胞瘤患者的数据，以揭示 TP53 和与 TP53 相关的基因的预后。
结果
高 TP53 mRNA 表达与小儿神经母细胞瘤的无事件生存和总生存缩短相关。此外，TP53 信号通路的富集评分较高与小儿神经母细胞瘤的临床结局较差相关。在与 TP53 相关的基因中，CCNE1、CDK2 和 CHEK2 与不良的临床结局相关，而 SESN1 与 8 个独立神经母细胞瘤队列中小儿神经母细胞瘤的有利临床结局相关。TP53、CCNE1、CDK2 和 CHEK2 在 MYCN 扩增的神经母细胞瘤患者中过表达，而 SESN1 在 MYCN 扩增的神经母细胞瘤患者中下调。CCNE1、SESN1、MYCN 扩增和诊断时的年龄是神经母细胞瘤的独立预后标志物。CCNE1 在诊断时年龄≥18 个月的小儿神经母细胞瘤患者中也高度表达，而 SESN1 在诊断时年龄≥18 个月的小儿神经母细胞瘤患者中下调。CCNE1 与年龄的组合或 SESN1 与年龄的组合在小儿神经母细胞瘤中取得了更好的预后效果。最后，我们基于年龄和 TP53、CCNE1、CDK2、CHEK2 和 SESN1 的表达构建了小儿神经母细胞瘤的列线图风险模型。该列线图模型能够预测小儿神经母细胞瘤和非 MYCN 扩增的小儿神经母细胞瘤的总生存，具有较高的特异性和敏感性。
结论
TP53 和与 TP53 相关的基因 CCNE1、CDK2、CHEK2 和 SESN1 与小儿神经母细胞瘤的临床结局显著相关。
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