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Upregulation of Hypoxia-Inducible Factor-1α mRNA and its Clinical Significance in Non-small Cell Lung Cancer

Background: Hypoxia-inducible factor 1α (HIF-1α) 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-1α in non-small cell lung cancer (NSCLC) tissues to clarify the impact on the clinical aspects of NSCLC patients. Experimental Design: HIF-1α 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-1α and clinicopathological factors was investigated. Results: The expression level of HIF-1α mRNA, which correlated with its protein level, was significantly higher in tumor tissue than in the corresponding nontumor-bearing lung tissue (4.22 × 104 ± 4.99 × 104 versus 1.24 × 104 ± 1.15 × 104; p < 0.001). The level of HIF-1α 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-1α mRNA in tumors were associated with a poor prognosis (p = 0.0401), but not in the node-positive cases. Conclusion: The expression of HIF-1α mRNA is associated with disease progression in NSCLC tissues, and is expected as a biomarker or therapeutic target.