Prognostic value of NUSAP1 in progression and expansion of glioblastoma multiforme

J Neurooncol. 2018 Nov;140(2):199-208. doi: 10.1007/s11060-018-2942-1. Epub 2018 Jul 11.

Abstract

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.

Keywords: Glioblastoma multiforme; NUSAP1; Prognostic factor; Survival.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation
  • Cohort Studies
  • G2 Phase
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glioblastoma / diagnosis*
  • Glioblastoma / metabolism*
  • Humans
  • Kaplan-Meier Estimate
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Prognosis
  • RNA, Messenger / metabolism
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • Microtubule-Associated Proteins
  • NUSAP1 protein, human
  • RNA, Messenger