Abstract #5553: Glycolytic ENO1 is a prognostic marker for oral squamous cell carcinoma
Authors: Li-Wha Wu
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Cancer cells preferentially use inefficient glycolysis for energy production, known as Warburg effect. Consistent with the notion, glycolytic genes are overexpressed in 24 types of human cancer, head and neck cancer included. ENO1 is one such gene and encodes enolase 1, converting 12-phosphoglycerate into phosphoenolpyruvate in glycolysis. Although ENO1 deregulation has been implicated in lung cancer, there was no study pertaining to its role in head and neck cancer. Oral sqaumous cell carcinoma is the most type of head and neck cancer in Taiwan. In this report, we analyzed ENO1 mRNA expression status in 45 surgical specimens including tumor (T) and adjacent normal (N) tissues and study clinical significance of this degulation in oral cancer. Semi-quantitative RT-PCR showed that ENO1 mRNA expressed was increased in 75% of the cancer specimens compared to their normal counterparts (T/N>1 in 30/45 patients). Twelve out of 30 such patients had increased ENO1 mRNA expression by 2 fold or greater (T/N\#8805;2). ENO1 mRNA expression increased with the clinical progression with a significance at stage IV. ENO1 mRNA expression status in 45 patients was divided into two groups, high (T/N\#8805;2) and low (T/N<2). The relationship of their clinicopathological characteristics and ENO1 mRNA expression was analyzed by Chi-square test. There was no statistical difference in age and tumor sites between two groups. By contrast, high ENO1 expression was significantly observed in patients with large primary tumors (p = 0.045), late clinical stages (p = 0.021), non-well differentiation (p = 0.016) or positive neck metastasis (p = 0.022). Kaplan-Meier survival curve analysis showed that high ENO1 group had significantly poorer OS and DFS than low group (p<0.05). Cox model univariate analysis indicates that high ENO1, positive neck metastasis, recurrence or late stage (stage III and IV) was significantly associated with poor OS (p < 0.05). In multivariate analysis, both ENO1 expression status and recurrence remained associated with OS (p < 0.05). Adjustified by recurrence, high ENO1 group are 5 times higher than low group to die from the disease. Adjustified by ENO1 expression, patients with recurrence are 3.4 times more likely to die from the disease than those without recurrence. We also analyzed the relation between ENO1 expression status and OS in late-stage (III and IV) patients using Cox model. We were able to find that late stage patients with high ENO1 expression had poor OS than those with low ENO1 (log rank test, p = 0.03). Hazard ratio for high ENO1 group is 3.3 times higher than low group. (p = 0.04). Cochran-Armitage trend test showed a positive association of high ENO1 expression with the severity of neck metastasis p = 0.03). Together, ENO1 mRNA expression status is a potential prognostic marker for clinical outcomes of oral cancer patients particularly for those at late stage.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5553.