Hypoxia-related molecules HIF-1α, CA9, and osteopontin

Abstract

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