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

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Pathology & Oncology Research

Abstract

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.

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Acknowledgements

This study was supported partially by Kaohsiung Medical University, Taiwan “Aim for the Top Universities Grant, grant No. KMU-TP104PR08, KMU-TP104G00, KMU-TP104G03, and KMU-TP104G04.”

Funding

This study was supported partially by Kaohsiung Medical University, Taiwan “Aim for the Top Universities Grant, grant No. KMU-TP104PR08, KMU-TP104G00, KMU-TP104G03, and KMU-TP104G04.”

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Author notes

  1. Yi-Ting Chen, Hung-Pei Tsai, Chee-Yin Chai and Aij-Lie Kwan contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yi-Ting Chen, Chun-Chieh Wu & Chee-Yin Chai

  2. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yi-Ting Chen & Chee-Yin Chai

  3. Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Yi-Ting Chen, Chee-Yin Chai & Aij-Lie Kwan

  4. Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Hung-Pei Tsai & Aij-Lie Kwan

  5. Department of Radiology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chiao-Yun Chen

  6. Department of Radiology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chiao-Yun Chen

  7. Center of Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan

    Chiao-Yun Chen & Chee-Yin Chai

  8. Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

    Chee-Yin Chai

  9. Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

    Aij-Lie Kwan

  10. Department of Neurosurgery, University of Virginia, Charlottesville, VA, USA

    Aij-Lie Kwan

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  1. Yi-Ting Chen
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  2. Hung-Pei Tsai
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  3. Chun-Chieh Wu
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Correspondence to Chee-Yin Chai or Aij-Lie Kwan.

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Ethical Approval

This study was approved by the Institutional Review Board of Kaohsiung Medical University Hospital, Taiwan (KMUH-IRB-20140169). The study is performed on unlinked specimen without patients’ personal identification and in accordance with the ethical standards laid down in the 1964 Helsinki Declaration and its later amendments.

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Chen, YT., Tsai, HP., Wu, CC. et al. High-level Sp1 is Associated with Proliferation, Invasion, and Poor Prognosis in Astrocytoma. Pathol. Oncol. Res. 25, 1003–1013 (2019). https://doi.org/10.1007/s12253-018-0422-8

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