Parodi Stefano, Ognibene Marzia, Haupt Riccardo, Pezzolo Annalisa
U.O. Epidemiologia e Biostatistica, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy.
U.O.C. Laboratorio Cellule Staminali Post Natali e Terapie Cellulari, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy.
Diagnostics (Basel). 2020 May 16;10(5):315. doi: 10.3390/diagnostics10050315.
Stage 4S neuroblastoma is a childhood cancer occurring in infants (<12 months at diagnosis) with metastases limited to liver, skin, and bone marrow (<10%). It is associated with an excellent outcome, due to its notable ability to undergo spontaneous regression without any therapeutic intervention. However, a subgroup of patients is doomed to relapse and eventually to die in spite of aggressive therapies. Stage 4S neuroblastoma shows characteristic hypermethylation of genes involved in the telomere maintenance, indicating that the dysregulation of these genes might serve as prognostic marker. The retinoblastoma tumor suppressor protein (RB)-E2F transcription factors pathway is one of the critical tumor-suppressor/oncogene pathways involved in regulating telomerase expression. We have interrogated in silicopublic neuroblastoma databases for regulators involved in the RB-E2F pathway especially for E2F factors themselves, and we identified the E2F transcription factor 3 (E2F3) expression as a potential prognostic marker in stage 4S neuroblastoma. In order to confirm this finding, we screened 38 paraffin-embedded tissue samples stage 4S neuroblastoma for E2F3 protein expression using immunofluorescence, and we observed that augmented expression was strongly associated with impaired event-free survival. These results indicate that E2F3 expression might serve as prognostic marker in patients with stage 4S disease.
4S期神经母细胞瘤是一种发生于婴儿（诊断时年龄<12个月）的儿童癌症，转移局限于肝脏、皮肤和骨髓（<10%）。由于其在无任何治疗干预的情况下具有显著的自发消退能力，其预后良好。然而，尽管进行了积极治疗，仍有一部分患者注定会复发并最终死亡。4S期神经母细胞瘤显示出参与端粒维持的基因具有特征性的高甲基化，表明这些基因的失调可能作为预后标志物。视网膜母细胞瘤肿瘤抑制蛋白（RB）-E2F转录因子途径是参与调节端粒酶表达的关键肿瘤抑制/癌基因途径之一。我们在计算机上查询了公开的神经母细胞瘤数据库，以寻找参与RB-E2F途径的调节因子，特别是E2F因子本身，并且我们确定E2F转录因子3（E2F3）的表达作为4S期神经母细胞瘤的潜在预后标志物。为了证实这一发现，我们使用免疫荧光法筛选了38例4S期神经母细胞瘤石蜡包埋组织样本中的E2F3蛋白表达，并且我们观察到表达增加与无事件生存期受损密切相关。这些结果表明，E2F3表达可能作为4S期疾病患者的预后标志物。
