Background. Stathmin 1 (STMN1), a marker for immature neurons and tumors, controls microtubule dynamics by destabilizing tubulin. It plays an essential role in cancer progression and indicates poor prognosis in several cancers. This potential protein has not been clarified in clinical patients with neuroblastoma. Therefore, this study aimed to assess the clinical significance and STMN1 function in neuroblastoma with and without MYCN amplification. Methods. Using immunohistochemical staining, STMN1 expression was examined in 81 neuroblastoma samples. Functional analysis revealed the association among STMN1 suppression, cellular viability, and endogenous or exogenous MYCN expression in neuroblastoma cell lines. Result. High levels of STMN1 expression were associated with malignant potential, proliferation potency, and poor prognosis in neuroblastoma. STMN1 expression was an independent prognostic factor in patients with neuroblastoma. Furthermore, STMN1 knockdown inhibited neuroblastoma cell growth regardless of endogenous and exogenous MYCN overexpression. Conclusion. Our data suggest that assessing STMN1 expression in neuroblastoma could be a powerful indicator of prognosis and that STMN1 might be a promising therapeutic candidate against refractory neuroblastoma with and without MYCN amplification.
背景:Stathmin 1(STMN1)作为未成熟神经元和肿瘤的标志物,通过破坏微管蛋白稳定性调控微管动力学。该蛋白在癌症进展中起关键作用,并在多种恶性肿瘤中提示不良预后。然而,其在神经母细胞瘤临床患者中的作用尚未明确。本研究旨在评估STMN1在伴或不伴MYCN扩增的神经母细胞瘤中的临床意义及功能机制。 方法:采用免疫组化染色检测81例神经母细胞瘤样本中STMN1的表达水平。通过功能实验分析神经母细胞瘤细胞系中STMN1抑制与细胞活性、内源性及外源性MYCN表达之间的关联。 结果:STMN1高表达与神经母细胞瘤的恶性潜能、增殖活性及不良预后显著相关。多因素分析显示STMN1表达是神经母细胞瘤患者的独立预后因素。此外,无论内源性或外源性MYCN是否过表达,敲低STMN1均能抑制神经母细胞瘤细胞生长。 结论:本研究提示STMN1表达可作为神经母细胞瘤预后的有效预测指标,且该蛋白可能成为治疗伴或不伴MYCN扩增的难治性神经母细胞瘤的潜在靶点。