Expression of CRM1 in human gliomas and its significance in p27 expression and clinical prognosis

Neurosurgery. 2009 Jul;65(1):153-9; discussion 159-60. doi: 10.1227/01.NEU.0000348550.47441.4B.

Abstract

Objective: Gliomas are the most common type of primary intracranial tumor. Although tumor grade predicts the clinical course of most patients, molecular characteristics of individual tumors have emerged as important prognostic factors for patients with gliomas. Reduced expression of p27 protein is known as an independent prognostic marker in a large variety of cancers and is associated with an unfavorable prognosis. It is believed that phosphorylation of p27 on Ser10 has been shown to be required for the binding of CRM1, a carrier protein for nuclear export. This study assessed whether CRM1, Ser10-phosphorylated p27, and p27 correlated with each other, with glioma pathological stage, and with patient outcome.

Methods: Immunohistochemical and Western blot analysis were performed in 70 cases of human gliomas and normal brain tissues. Survival analyses were performed using the Kaplan-Meier method.

Results: High CRM1 expression (80% of cancer cell nuclei stained) was observed in 70 specimens and was related to the grade of malignancy. A strong inverse correlation was evident between p27 levels and both Ser10-phosphorylated p27 (P < 0.001) and CRM1 level (P < 0.001). We also reviewed each grade of tumors separately and investigated whether CRM1 expression predicted patient survival within each subgroup. In brief, CRM1 overexpression was significantly associated with overall survival (P < 0.001).

Conclusion: The current results showed that CRM1 and p27 expression were associated with glioma grade and that high CRM1 protein expression might be related to poor outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioma / diagnosis
  • Glioma / genetics
  • Glioma / metabolism*
  • Humans
  • Karyopherins / genetics
  • Karyopherins / metabolism*
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Retrospective Studies
  • Serine / genetics
  • Young Adult

Substances

  • Karyopherins
  • Ki-67 Antigen
  • Receptors, Cytoplasmic and Nuclear
  • exportin 1 protein
  • Cyclin-Dependent Kinase Inhibitor p27
  • Serine