Geminin: a good prognostic factor in high-grade astrocytic brain tumors

Cancer. 2007 Mar 1;109(5):949-56. doi: 10.1002/cncr.22474.

Abstract

Background: Geminin is a nuclear protein that belongs to the DNA replication inhibitor group. It inhibits DNA replication by preventing Cdt1 from loading minichromosome maintenance protein onto chromatin, as is required for DNA replication. For this study, the authors investigated geminin expression in high-grade astrocytic tumors, including anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM), with a view to predicting clinical outcomes on this basis in patients with these malignant brain tumors.

Methods: Immunohistochemistry was used to detect geminin expression in 51 patients with high-grade astrocytic tumors (19 AA and 32 GBM). Samples were categorized by taking the median value as the cut-off point for constructing Kaplan-Meier curves. The relation of geminin expression to clinical outcome in these malignant brain tumors was analyzed by using the Kaplan-Meier method and a Cox proportional hazards regression model.

Results: Geminin was expressed in all high-grade astrocytomas (mean geminin labeling index [LI], 24.90%). Kaplan-Meier curves showed that the group with higher geminin LI (>or=22.50%) had a better prognosis than the group with lower LI (<22.50%; P = .0296). Similarly, the Cox regression analysis showed that geminin expression has a significant correlation with survival in patients with high-grade astrocytoma (P = .0278), especially in an early stage.

Conclusions: Although it is an inhibitor of DNA proliferation and, thus, is a cell cycle inhibitor, geminin expression was found in all malignant astrocytic tumors. The geminin LI was a significant predictive factor of outcomes in patients with high-grade astrocytoma, with higher expression indicating a good prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Astrocytoma / metabolism*
  • Astrocytoma / mortality
  • Astrocytoma / pathology
  • Biomarkers, Tumor / analysis*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Cell Cycle Proteins / metabolism*
  • Child
  • Female
  • Geminin
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Prognosis
  • Survival Analysis

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • GMNN protein, human
  • Geminin