- Prognostic Significance of Glycolytic Metabolic Change Related to HIF-1alpha in Oral Squamous Cell Carcinomas.
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Sook Hee Hong, 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
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Korean J Pathol. 2010;44(4):360-369.
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DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.4.360
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 Abstract
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- 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.
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Citations
Citations to this article as recorded by  - Glucose transporter 1 (GLUT1) of anaerobic glycolysis as predictive and prognostic values in neoadjuvant chemoradiotherapy and laparoscopic surgery for locally advanced rectal cancer
Byoung Yong Shim, Ji-Han Jung, Kang-Moon Lee, Hyung-Jin Kim, Sook Hee Hong, Sung Hwan Kim, Der Sheng Sun, Hyeon-Min Cho
International Journal of Colorectal Disease.2013; 28(3): 375. CrossRef
- Expressions of Cyclin E-pathway Proteins (cyclinE, cdk2, p21, p27, p57) and Their Prognostic Significance in Non-small Cell Lung Carcinomas.
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Ji Han Jung, Gyeongsin Park, Myung Ah Lee, Jae Ho Byun, Chan Kwon Jung, Heejeong Lee, Kyo Young Lee, Sang In Shim, Chang Suk Kang
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Korean J Pathol. 2006;40(1):24-31.
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Abstract
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- BACKGROUND
The aberrant expression of cyclins, cdk and cdk inhibitor has been shown to be involved in oncogenic transformation. The aim of this study was to investigate the expression of the cyclin E-pathway proteins (cyclin E, cdk2, p21, p27, p57) in human non-small cell lung carcinomas (NSCLC) and also to evaluate the clinical significance of these expressions.
METHODS
A total of 203 consecutive patients with completely resected pathological stage I-III NSCLC were retrospectively reviewed. The expressions of cyclin E, cdk2, p21, p27 and, p57 was examined by performing immunohistochemistry with using the tissue microarray method.
RESULTS
In the total cases, the expression levels of cyclin E, cdk2, p21, p27 and p57 were 39.9% (81/203), 48.3% (98/203), 68.0% (138/203), 32.5% (66/203) and 2.7% (5/203), respectively. The overexpression of cyclin E and cdk2 was significantly and inversely correlated with the histologic differentiation in the adenocarcinoma (p<0.05), but not in the squamous cell carcinoma. Among the clinicopathologic factors, the stage and lymph node metastasis were associated with overall survival (p<0.05). Among these proteins, the negative expression of p21 was significantly correlated with a shortened survival rate (p<0.05).
CONCLUSIONS
These data suggest that the overexpression of cyclin E and cdk2 and the loss of p21 and p27 are associated with tumor progression in NSCLC. The aberrant expression of p21 is correlated with a poor prognosis. Therefore the immunohistochemical analysis of this protein as well as the clinical stage and, lymph node metastasis may be useful tools for evaluating the prognosis of NSCLC patients.
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