Upregulation of hypoxia-inducible factor-1alpha mRNA and its clinical significance in non-small cell lung cancer.

ABSTRACT

BACKGROUND: Hypoxia-inducible factor 1alpha (HIF-1alpha) is a transcription factor that plays an important role in tumor growth by regulating the energy metabolism and angiogenesis. We herein investigated the mRNA expression level of HIF-1alpha in non-small cell lung cancer (NSCLC) tissues to clarify the impact on the clinical aspects of NSCLC patients. EXPERIMENTAL DESIGN: HIF-1alpha mRNA derived from either a tumor or an adjacent lung tissue was quantified using quantitative reverse transcription polymerase chain reaction in 66 patients with NSCLC. The relationship between the mRNA expression level of HIF-1alpha and clinicopathological factors was investigated. RESULTS: The expression level of HIF-1alpha mRNA, which correlated with its protein level, was significantly higher in tumor tissue than in the corresponding nontumor-bearing lung tissue (4.22 x 10(4) +/- 4.99 x 10(4) versus 1.24 x 10(4) +/- 1.15 x 10(4); p < 0.001). The level of HIF-1alpha mRNA showed a significantly positive correlation with the mRNA levels of vascular endothelial growth factor and type II hexokinase in tumors (p < 0.0001 for each). In node-negative patients, high expression levels of HIF-1alpha mRNA in tumors were associated with a poor prognosis (p = 0.0401), but not in the node-positive cases. CONCLUSION: The expression of HIF-1alpha mRNA is associated with disease progression in NSCLC tissues, and is expected as a biomarker or therapeutic target.