Prognostic Significance of Glycolytic Metabolic Change Related to HIF-1alpha in Oral Squamous Cell Carcinomas.
- Author:
Sook Hee HONG
1
;
Sang Young ROH
;
Yoon Ho KO
;
Hye Sung WON
;
Myung Ah LEE
;
In Sook WOO
;
Jae Ho BYUN
;
Jin Hyoung KANG
;
Young Seon HONG
;
Chan Kwon JUNG
;
Yeon Sil KIM
;
Young Hoon JU
;
Min Sik KIM
Author Information
1. Division of Medical Oncology, Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
Carcinoma, squamous cell;
HIF1A protein, human;
Lactate dehydrogenase 5;
Pyruvate dehydrogenase (acetyl-transferring) kinase
- MeSH:
Biomarkers;
Carcinoma, Squamous Cell;
Disease-Free Survival;
Glycolysis;
Humans;
Hypoxia-Inducible Factor 1, alpha Subunit;
Isoenzymes;
L-Lactate Dehydrogenase;
Oxidoreductases;
Phenotype;
Phosphotransferases;
Prognosis;
Protein-Serine-Threonine Kinases;
Pyruvic Acid;
Recurrence;
Up-Regulation
- From:Korean Journal of Pathology
2010;44(4):360-369
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Growing tumors adapt to a hypoxic environment and increase anaerobic glycolysis. This metabolic switch is related to aggressive behavior. We investigated the relationship between glycolytic metabolism biomarkers associated with hypoxia-inducible factor (HIF)-1alpha and prognosis. METHODS: We performed immunohistochemical staining of HIF-1alpha, pyruvate dehydrogenase kinase (PDK) 1 and lactate dehydrogenase (LDH) 5 in 74 patients with oral squamous cell carcinoma (SCC) who had received curative radical resection. RESULTS: High reactivity of HIF-1alpha, PDK 1 and LDH 5 was observed in 29 (39.2%), 32 (43.2%) and 54 (73.0%) patients, respectively. Expression levels of the three biomarkers were significantly correlated. All three markers were highly expressed in 16 (21.6%) patients. Elevated expression of the three markers was associated with increased invasiveness (p = 0.043) and recurrence (p = 0.017) of tumors. In survival analysis, upregulation of the three markers was additionally associated with shorter disease free survival (DFS, p = 0.001) and overall survival (OS, p = 0.002). High expression of all three markers was a strong independent prognostic factor for DFS (p = 0.030) and OS (p = 0.026). CONCLUSIONS: Oral SCC with altered glycolytic metabolism exhibits a more invasive and aggressive phenotype. Our results indicate that glycolytic metabolism biomarkers related to HIF-1alpha may be independent prognostic factors in patients with oral SCC.
