Association between expression of transcription factor Sp1 and increased vascular endothelial growth factor expression, advanced stage, and poor survival in patients with resected gastric cancer.
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.
Yao
James C
JC
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Wang
Liwei
L
Wei
Daoyan
D
Gong
Weida
W
Hassan
Manal
M
Wu
Tsung-Teh
TT
Mansfield
Paul
P
Ajani
Jaffer
J
Xie
Keping
K
D000368:Aged; D015153:Blotting, Western; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D016329:Sp1 Transcription Factor / Q000096:biosynthesis*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality*; D013997:Time Factors; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
D016329:Sp1 Transcription Factor; D042461:Vascular Endothelial Growth Factor A