Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, 1055 Sanxiang Rd, Suzhou, 215004, China.
Department of Neurosurgery, Clinical Medical College of Yangzhou University, 98 Nantong West-Road, Yangzhou, 225001, China.
J Neurooncol. 2018 Nov;140(2):199-208. doi: 10.1007/s11060-018-2942-1. Epub 2018 Jul 11.
Nucleolar and spindle-associated protein (NUSAP1) is a microtubule and chromatin-binding protein that stabilizes microtubules to prevent depolymerization, maintains spindle integrity. NUSAP1 could cross-link spindles into aster-like structures, networks and fibers. It has also been found to play roles in progression of several cancers. However, the potential correlation between NUSAP1 and clinical outcome in patients with glioblastoma multiforme (GBM) remains largely unknown. In the current study, we demonstrated that NUSAP1 was significantly up-regulated in GBM tissues compared with adult non-tumor brain tissues both in a validated cohort and a TCGA cohort. In addition, Kaplan-Meier analysis indicated that patients with high NUSAP1 expression had significantly lower OS (P = 0.0027). Additionally, in the TCGA cohort, NUSAP1 expression was relatively lower in GBM patients within the neural and mesenchymal subtypes compared to other subtypes, and associated with the status of several genetic aberrations such as PTEN deletion and wild type IDH1. The present study provides new insights and evidence that NUSAP1 over-expression was significantly correlated with progression and prognosis of GBM. Furthermore, knockdown of NUSAP1 revealed its regulation on G2/M progression and cell proliferation (both in vitro and in vivo). These data demonstrate that NUSAP1 could serve as a novel prognostic biomarker and a potential therapeutic target for GBM.
核仁与纺锤体相关蛋白(NUSAP1)是一种微管和染色质结合蛋白,它稳定微管以防止解聚,维持纺锤体的完整性。NUSAP1 可以将纺锤体交联成星状结构、网络和纤维。它还被发现参与了几种癌症的进展。然而,NUSAP1 与胶质母细胞瘤(GBM)患者临床结局之间的潜在相关性在很大程度上仍不清楚。在本研究中,我们证明与成人非肿瘤脑组织相比,NUSAP1 在验证队列和 TCGA 队列的 GBM 组织中均显著上调。此外,Kaplan-Meier 分析表明,高表达 NUSAP1 的患者 OS 明显降低(P=0.0027)。此外,在 TCGA 队列中,与其他亚型相比,神经和间质亚型的 GBM 患者中 NUSAP1 的表达相对较低,与几种遗传异常的状态相关,如 PTEN 缺失和野生型 IDH1。本研究提供了新的见解和证据,表明 NUSAP1 的过表达与 GBM 的进展和预后显著相关。此外,敲低 NUSAP1 显示其对 G2/M 进展和细胞增殖(体内外)的调节作用。这些数据表明,NUSAP1 可以作为 GBM 的新型预后生物标志物和潜在的治疗靶点。