U.O.C. Genetica Medica, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Unità di Bioinformatica Clinica, Direzione Scientifica, IRCCS Istituto Giannina Gaslini, Genova, Italy.
Pediatr Blood Cancer. 2022 Oct;69(10):e29800. doi: 10.1002/pbc.29800. Epub 2022 Jun 2.
Neuroblastoma (NB) is an enigmatic childhood malignancy characterised by a wide range of clinical behaviour. Many potential oncogenes for NB have recently been identified. Among them, E2 transcription factor 3 (E2F3) expression was associated with a poor survival in 134 stage 4S patients, but evidence for other stage groups remains poorly investigated.
We have analysed the expression of E2F3 gene from a database of 786 NB samples. Overall and event-free survivals (EFS) were assessed by the Kaplan-Meier method, splitting the data on the median and tertile expression values. The Cox model was applied to control for the confounding by stage, age and MYCN amplification. Validation was performed by an in silico analysis of an independent cohort of 283 NB patients. Furthermore, an immunofluorescence analysis on 48 formalin-fixed, paraffin-embedded NB specimens was also performed.
E2F3 overexpression was associated with a poor survival (EFS = 84%, 95% CI: 79%-95%, for low expression levels; EFS = 62%, 95% CI: 56%-68% for middle levels; EFS = 30%, 95% CI: 24%-36%, for high levels, p < .001). This association was confirmed in multivariable analysis and was more evident in patients with MYCN not-amplified and localised stages. Immunofluorescence results and the validation on an independent cohort of NB primary samples confirmed these findings.
E2F3 is a new potential prognostic marker in NB with favourable characteristics at diagnosis. Further studies are needed to elucidate the potential role of E2F3 in NB oncogenesis and progression, in order to identify new targets for therapeutic interventions.
神经母细胞瘤（NB）是一种具有广泛临床行为的神秘儿童恶性肿瘤。最近已经确定了许多 NB 的潜在癌基因。其中，E2 转录因子 3（E2F3）的表达与 134 例 4S 期患者的不良生存相关，但其他分期组的证据仍未得到充分研究。
我们从 786 例 NB 样本的数据库中分析了 E2F3 基因的表达。通过 Kaplan-Meier 法评估总体生存率（OS）和无事件生存率（EFS），将数据按中位数和三分位值进行划分。Cox 模型用于控制分期、年龄和 MYCN 扩增的混杂因素。通过对 283 例 NB 患者的独立队列进行计算机分析来进行验证。此外，还对 48 例福尔马林固定、石蜡包埋的 NB 标本进行了免疫荧光分析。
E2F3 过表达与不良生存相关（EFS=84%，95%CI：79%-95%，低表达水平；EFS=62%，95%CI：56%-68%，中表达水平；EFS=30%，95%CI：24%-36%，高表达水平，p<0.001）。该关联在多变量分析中得到了证实，并且在 MYCN 未扩增和局部分期的患者中更为明显。免疫荧光结果和对 NB 原发性样本的独立队列的验证证实了这些发现。
E2F3 是 NB 中的一个新的潜在预后标志物，具有良好的诊断特征。需要进一步研究以阐明 E2F3 在 NB 发生和进展中的潜在作用，以确定治疗干预的新靶点。
