The
biological and clinical behaviors of
cancer are affected by multiple molecular pathways that are under the control of
transcription factors. Improved understanding of how
transcription factors affect
cancer biology may lead to improved ability to predict clinical outcome and discovery of novel therapeutic strategies. We evaluated the relationship between Sp1 and
vascular endothelial growth factor (
VEGF) expression, as well as their effect on survival in 86 cases of resected human
gastric cancer. The degree of
VEGF expression correlated highly with Sp1 expression (P < 0.01). Patients with high Sp1 expression were 98 times more likely to have high
VEGF expression compared with those with negative Sp1 expression. Clinically, negative or weak Sp1 expression was associated with early stage (IA) in
gastric cancer. Strong Sp1 expression was more frequently observed among patients with stage IB-IV disease (P = 0.035). Similarly, whereas strong Sp1 expression was uncommonly observed among patients with N0 or N1 disease (19 and 16%), N2/N3
gastric cancer was associated with strong Sp1 expression (48%; P = 0.034). Strong Sp1 expression was also associated with inferior survival. The median survival duration in patients who had a
tumor with a negative, weak, and strong Sp1 expression was 44, 38, and 8 months (P = 0.0075), respectively, whereas patients with strong
VEGF expression had a shorter survival duration; the difference was not statistically significant. When Sp1 and
VEGF expression, stage, completeness of resection, histology, and patient age were entered in a Cox proportional hazards model, strong Sp1 expression (P = 0.021) and an advanced disease stage (P < 0.001) were independently prognostic of poor survival. Given the importance of Sp1 in the expression of
VEGF, our data suggest that dysregulated Sp1 expression and activation play important roles in
VEGF overexpression and, thus,
gastric cancer development and progression.