Prognostic value of facilitative glucose transporter Glut-1 in oral squamous cell carcinomas treated by surgical resection

Oliver, Richard; Woodwards, R.T.; Sloan, Philip; Thakker, Nalin; Stratford, Ian J.; Airley, Rachel

doi:10.1016/j.ejca.2003.10.024

Cited by 78 publications

(58 citation statements)

References 19 publications

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“…Although the results were not statistically significant (p＞0.05), the group with a high Glut-1 expression had a better disease-free survival. These findings are consistent with previous reports about the prognostic value of the Glut-1 expression for oral squamous cell carcinoma (4,7). Oral squamous cell carcinoma with the overexpression of Glut-1 has demonstrated high fluorine-18 fluoro-2 deoxy-D-glucose (FDG) uptake, although there was no proven correlation between FDG SUV and the Glut-1 expression (8).…”

Section: Discussionsupporting

confidence: 82%

“…In this study, we analyzed patients with squamous cell carcinoma of the tongue because most previous studies were performed with various kinds of the head and neck squamous cell carcinomas such as larynx, pharynx, nasal cavity and the floor of the mouth (4,7,13,14). Thus, our study focused on one site of the head and neck to exclude the bias associated with the location of primary lesion.…”

Section: Discussionmentioning

confidence: 99%

“…The up-regulated glycolytic metabolism may represent a compensatory change that allows for adaptation of proliferating tumor cells under adverse conditions, and this is primarily mediated by glucose transporters. Glucose transporter-1 (Glut-1) is one of the glucose transporters expressed in many tumors, and it has shown a correlation with a poor prognosis (3,4). The expression of Glut-1 may allow for the continuous growth of tumor cells under hypoxic conditions.…”

Section: Introductionmentioning

confidence: 99%

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Glucose Transporter-1 Expression in Squamous Cell Carcinoma of the Tongue

Choi

Kim

et al. 2007

Cancer Res Treat

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Purpose: Tumor cells are known to express hypoxia-related proteins such as glucose transporter-1 (Glut-1). These hypoxia-induced changes may allow tumor cells to survive under sustained hypoxic microenvironments, and the surviving tumor cell under hypoxia may develop a more aggressive phenotype and so result in a poor prognosis.Materials and Methods: The Glut-1 expression was analyzed by immunohistochemistry, and its association with the prognosis was assessed in 60 patients with squamous cell carcinoma of the tongue.Results: The Glut-1 expression was diffuse with a membranous pattern, and the median percentage of Glut-1 positive tumor cells was 60% (range: 0.0∼ 90.0%). A high Glut-1 expression (the percentage of positive tumor cells ≥ the median value, 60%) was associated with the location of primary lesion, lymph node me ta sta sis sta tus a nd dise a se sta ge (p＜0 .0 5 ) .The expression of Glut-1 was correlated with the Ki-67 expression (r=0.406, p=0.001). Microvessel density, as represented by CD31 staining, was also correlated with the Glut-1 expression although its significance is weak (r=0.267, p=0.039). On the univariate analysis, the group with a high Glut-1 expression showed poorer overall survival than the group with a low Glut-1 expression (p ＜0.05). However, the Glut-1 expression failed to show any independent prognostic significance on the multivariate analysis.Conclusion

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glucose Transporter-1 Expression in Squamous Cell Carcinoma of the Tongue

Choi

Kim

et al. 2007

Cancer Res Treat

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“…oncomine.org), all but one of the 15 top-ranked (by pĈ score) genes showed prognostic significance in at least one tumour site (Po0.0001). The only top gene for which prognostic significance was not reported in Oncomine, SLC2A1 (GLUT1), is prognostic in other studies (Oliver et al, 2004). Finally, cumulative forest plots based on connectivity score (Figure 3) showed no further improvement in HR after addition of a small number of genes.…”

Section: A Common Hypoxia Metagene Across Cancer Typesmentioning

confidence: 87%

Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene

et al. 2010

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BACKGROUND: There is a need to develop robust and clinically applicable gene expression signatures. Hypoxia is a key factor promoting solid tumour progression and resistance to therapy; a hypoxia signature has the potential to be not only prognostic but also to predict benefit from particular interventions. METHODS: An approach for deriving signatures that combine knowledge of gene function and analysis of in vivo co-expression patterns was used to define a common hypoxia signature from three head and neck and five breast cancer studies. Previously validated hypoxia-regulated genes (seeds) were used to generate hypoxia co-expression cancer networks. RESULTS: A common hypoxia signature, or metagene, was derived by selecting genes that were consistently co-expressed with the hypoxia seeds in multiple cancers. This was highly enriched for hypoxia-regulated pathways, and prognostic in multivariate analyses. Genes with the highest connectivity were also the most prognostic, and a reduced metagene consisting of a small number of topranked genes, including VEGFA, SLC2A1 and PGAM1, outperformed both a larger signature and reported signatures in independent data sets of head and neck, breast and lung cancers. CONCLUSION: Combined knowledge of multiple genes' function from in vitro experiments together with meta-analysis of multiple cancers can deliver compact and robust signatures suitable for clinical application.

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“…Actually, Glut1 protein expression confers poor prognosis in a wide range of solid tumors. 11,12 Studies regarding GLUT1 expression in HCC have revealed inconclusive results, and the biological significance of GLUT1 expression in HCC remains unknown. [13][14][15][16][17][18][19] Here, we show that GLUT1 expression is increased in a significant number of HCC cell lines and tissues, and high GLUT1 expression correlates with HCC proliferation and invasiveness.…”

mentioning

confidence: 99%

GLUT1 Expression Is Increased in Hepatocellular Carcinoma and Promotes Tumorigenesis

Amann

Maegdefrau

Hartmann

et al. 2009

The American Journal of Pathology

292

217

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Accelerated glycolysis is one of the biochemical characteristics of cancer cells. The glucose transporter isoform 1 (GLUT1) gene encodes a key rate-limiting factor in glucose transport into cancer cells. However, its expression level and functional significance in hepatocellular cancer (HCC) are still disputed. Therefore, we aimed to analyze the expression and function of the GLUT1 gene in cases of HCC. We found significantly higher GLUT1 mRNA expression levels in HCC tissues and cell lines compared with primary human hepatocytes and matched nontumor tissue. Immunohistochemical analysis of a tissue microarray of 152 HCC cases revealed a significant correlation between Glut1 protein expression levels and a higher Ki-67 labeling index, advanced tumor stages, and poor differentiation. Accordingly, suppression of GLUT1 expression by siRNA significantly impaired both the growth and migratory potential of HCC cells. Furthermore, inhibition of GLUT1 expression reduced both glucose uptake and lactate secretion. Hypoxic conditions further increased GLUT1 expression levels in HCC cells , and this induction was dependent on the activation of the transcription factor hypoxiainducible factor-1␣. In summary , our findings suggest that increased GLUT1 expression levels in HCC cells functionally affect tumorigenicity , and thus , we propose GLUT1 as an innovative therapeutic target for this highly aggressive tumor. (Am J Pathol

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Prognostic value of facilitative glucose transporter Glut-1 in oral squamous cell carcinomas treated by surgical resection

Cited by 78 publications

References 19 publications

Glucose Transporter-1 Expression in Squamous Cell Carcinoma of the Tongue

Glucose Transporter-1 Expression in Squamous Cell Carcinoma of the Tongue

Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene

GLUT1 Expression Is Increased in Hepatocellular Carcinoma and Promotes Tumorigenesis

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