Overexpression of Fli-1 in astrocytoma is associated with poor prognosis

// Hung-Pei Tsai 1 , Tai-Hsin Tsai 2, 3 , Ya-Ju Hsieh 4 , Yi-Ting Chen 5 , Chih-Ling Lee 5 , Yi-Cheng Tsai 1 , Ting-Chang She 5 , Chih-Lung Lin 2, 3 , Chee-Yin Chai 5, 6, 7 , Aij-Lie Kwan 2, 3, 8 1 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 3 Department of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 4 Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 6 Department of Pathology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 7 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan 8 Department of Neurosurgery, University of Virginia, Charlottesville, VA, USA Correspondence to: Aij-Lie Kwan, email: a_lkwan@yahoo.com Chee-Yin Chai, email: ccjtsai@yahoo.com Keywords: astrocytoma, Fli-1, prognostic marker Received: June 29, 2016 Accepted: February 20, 2017 Published: March 16, 2017 ABSTRACT Background: Astrocytoma, a common and highly malignant type of brain tumor, is associated with poor overall survival despite advances in surgical treatment, radiotherapy, and chemotherapy. The nuclear transcription factor Fli-1 has been shown to increase cellular proliferation and tumorigenesis in many types of cancer; however, previous reports have not described a correlation between clinical outcomes and Fli-1 in astrocytoma patients. The present study aimed to elucidate the clinical role of Fli-1 in astrocytoma. Results: High-level of Fli-1 protein expression was significantly association with World Health Organization (WHO) high grade and poor prognosis. A multivariate analysis revealed that the WHO grade and Fli-1 protein expression were independent factor of prognostic factors of patients with astrocytoma. In addition, Fli-1 silencing inhibited proliferation, migration, and invasion and led to the downregulation of Ki-67, VEGF, and cyclin D1 expression in the astrocytoma cells. Materials and methods: Fli-1 protein expression in astrocytoma tissue samples were detected via immunohistochemistry, and potential correlations between clinical parameters and Fli-1 expression were assessed in patients with astrocytoma. Additionally, proliferation, invasion, and migration assays of astrocytoma cell lines were conducted to evaluate the effects of short interfering RNA (siRNA) on these processes; in addition, these cells were subjected to western blotting to detect the expression levels of Fli-1, Ki-67, VEGF, and Cyclin D1. Conclusion: Fli-1 shows promise as a potential prognostic biomarker and therapeutic molecular target for astrocytoma patients.