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

J Thorac Oncol. 2009 Mar;4(3):284-90. doi: 10.1097/JTO.0b013e31819852d5.

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.

Publication types

  • Comparative Study

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cohort Studies
  • Disease Progression
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Immunohistochemistry
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Male
  • Neoplasm Staging
  • Probability
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Survival Analysis
  • Tissue Culture Techniques
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Biomarkers, Tumor
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • RNA, Messenger
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A