Hypoxia-related molecules HIF-1α, CA9, and osteopontin : predictors of survival in patients with high-grade glioma

Strahlenther Onkol. 2013 Feb;189(2):147-54. doi: 10.1007/s00066-012-0262-5. Epub 2012 Dec 22.

Abstract

Purpose: A high expression of hypoxia-inducible factor-1 alpha (HIF)-1α, carbonic anhydrase 9 (CA9), and osteopontin appears to be a strong prognostic indicator in many malignancies; however, their role is unclear in high-grade gliomas.

Patients and methods: HIF-1α, CA9, and osteopontin levels in tissue specimens of 92 patients with high-grade glioma were evaluated by immunohistochemistry.

Results: Patients with a high expression of cytoplasmic and nuclear HIF-1α, CA9, and osteopontin had significantly shorter overall survival. The expression results of these markers were combined to form a hypoxic profile, and high hypoxic scores (expression of two or three markers) were significantly correlated to poorer overall survival. In multivariate analysis, high hypoxic score-1 (cytoplasmic HIF-1α, CA9, and osteopontin) was the only independent negative prognostic factor for survival (p = 0.028).

Conclusion: Our results showed that a combination of hypoxic markers is more robust than a single marker for predicting survival in high-grade glioma. It may be necessary to utilize the hypoxic score in selecting patients for targeted therapy in the future.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, Neoplasm / analysis*
  • Biomarkers, Tumor / analysis*
  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / mortality*
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / analysis*
  • Cell Hypoxia
  • Female
  • Glioma / diagnosis
  • Glioma / metabolism
  • Glioma / mortality*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / analysis*
  • Male
  • Middle Aged
  • Osteopontin / analysis*
  • Prevalence
  • Reproducibility of Results
  • Risk Factors
  • Sensitivity and Specificity
  • Survival Analysis*
  • Survival Rate
  • Turkey / epidemiology
  • Young Adult

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Osteopontin
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases