High-level Sp1 is Associated with Proliferation, Invasion, and Poor Prognosis in Astrocytoma

Astrocytoma is the most common and the most lethal primary brain tumor in adults. Grade IV glioblastoma is usually refractory to currently available surgical, chemotherapeutic, and radiotherapeutic treatments. The Specificity protein 1 (Sp1) transcription factor is known to regulate tumorigenesis in many cancers. The aim of this study was to investigate the clinicopathologic role of Sp1 protein in the carcinogenesis of astrocytoma. This study analyzed 98 astrocytoma cases treated at Kaohsiung Medical University Hospital during 2002-2012. Clinicopathologic parameters associated with Sp1 were analyzed by chi-square test, Kaplan-Meier analysis, and Cox regression analyses. In vitro proliferation, invasion, and migration were compared between non-siRNA groups and Sp1 siRNA groups. In glioblastoma cells treated with Sp1 siRNA, Western blot was also used to detect expressions of Sp1, Ki-67, VEGF, cyclin D1, E-cadherin, cleaved caspase-3 and Bax proteins. Expression of Sp1 was significantly associated with WHO grade (p = 0.005) and with overall survival time (p < 0.001). Multivariate analysis further revealed that prognosis of astrocytoma was significantly associated with Sp1 expression (p = 0.036) and IDH-1 expression (p < 0.001). In vitro silencing of Sp1 downregulated Sp1, Ki-67, and cyclin D1 but upregulated E-cadherin, Bax, and cleaved caspase-3. These data suggest that Sp1 is a potential prognostic marker and therapeutic target in astrocytoma.