Altered Expression of Transcription Factor Sp1 Critically Impacts the Angiogenic Phenotype of Human Gastric Cancer

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Abstract
Our recent study has shown that transcription factor Sp1 is an independent prognostic factor in gastric cancer. However, it is unclear how Sp1 impacts gastric cancer biology. Since Sp1 regulates multiple genes important to angiogenesis, we sought to evaluate the relationship between Sp1 expression and microvessel density (MVD) as well as their effects on cancer patient survival. The expression of Sp1 and status of MVD was determined using archival tissues of 86 cases of resected human gastric cancer. We found that MVD correlated highly with Sp1 expression (P < 0.001). Patients with strong Sp1 expression were 12 times more likely to have high MVD than were those with negative Sp1 expression. In univariate survival analyses, both elevated Sp1 expression (P = 0.007) and high MVD expression (P = 0.036) were associated with inferior survival. However, when Sp1 expression, MVD expression, disease stage, completeness of resection, Lauren’s classification, and patient age were entered into a Cox proportional hazards model, only strong Sp1 expression (P = 0.047) and advanced stage (P < 0.01) were independently prognostic of poor survival. Furthermore, knocking down Sp1 expression significantly impaired the angiogenic potential of tumor cells in vitro and suppressed angiogenesis in vivo animal models. Therefore, we provided both clinical and experimental evidence to indicate that Sp1 might impact gastric cancer development and progression through regulating angiogenesis, a critical aspect of cancer biology.