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


METHODS
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.


CONCLUSIONS
The expression of HIF-1alpha mRNA is associated with disease progression in NSCLC tissues, and is expected as a biomarker or therapeutic target.
Yohena
Tomofumi
T
Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.
Yoshino
Ichiro
I
Takenaka
Tomoyoshi
T
Kameyama
Toshifumi
T
Ohba
Taro
T
Kuniyoshi
Yukio
Y
Maehara
Yoshihiko
Y
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D046509:Tissue Culture Techniques; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A