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Elevated E2F7 expression predicts poor prognosis in human patients with gliomas
Affiliation:1. The First People’s Hospital of Xuzhou, No.19, North Zhongshan Road, Quanshan District, Xuzhou, Jiangsu Province 221002, China;2. Department of Neurosurgery, XuZhou Central Hospital, Xuzhou, China;1. Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China;2. Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China;3. Department of Radiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA;4. Department of Pathology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA;5. Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA;6. Department of Radiology, Brigham and Women''s Hospital, Boston, Massachusetts, USA;7. Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA;1. Department of Surgery, Yale School of Medicine, New Haven, Connecticut;2. University of Zurich, Zurich, Switzerland;3. Division of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, Connecticut;4. Department of Genetics, Yale School of Medicine, New Haven, Connecticut;5. Section of Surgical Oncology, Department of Surgery, Yale School of Medicine, New Haven, Connecticut;1. Technion Israel Institute of Technology, Haifa, Israel;2. Department of Hematology, Rambam Health Care Campus, Haifa, Israel;3. Northwestern University Feinberg School of Medicine, Chicago, IL, USA;4. Department of Hematology, Shaare Zedek Medical Center, Jerusalem, Israel
Abstract:E2F transcription factors have been studied extensively in a broad range of organisms as major regulators of cell cycle, apoptosis, and differentiation. The E2F family includes the atypical member E2F7, which has been rarely studied in gliomas. The aim of this study is to determine the expression status of E2F7 in gliomas, its relationship to clinicopathological features, and patients’ outcome. The mRNA levels of E2F7 in the human brain and different grades of gliomas were analysed using datasets from the publically available Oncomine database. One of the most significant co-expression factors, CDK1, together with E2F7, was further validated by immunohistochemistry in 90 different grades of gliomas. Furthermore, univariate and multivariate analyses were performed to identify prognostic variables relative to patient and tumour characteristics and treatment modalities. E2F7 mRNA expression was found to be elevated in gliomas by Oncomine-database analysis. Immunohistochemistry showed an increase in E2F7 labelling index in high- versus low-grade gliomas (62.1 ± 11.8% vs. 18.9 ± 10.2%, p < 0.0001). There was a positive correlation between E2F7 and CDK1 immunoreactivity (Spearman r = 0.446, p = 0.037). Clinicopathological evaluation suggested that E2F7 expression was associated with tumour grade (p < 0.0001) and recurrence (p = 0.025). In Cox multivariate analysis, pathological classification and recurrence were independent prognostic factors of gliomas, and E2F7 was significantly related to progression-free survival (p = 0.011), but not overall survival (p = 0.062). Our findings suggested that E2F7 might act as an independent prognostic factor of gliomas and might constitute a potential therapeutic target for this disease.
Keywords:CDK1  E2F7  Glioma  Prognosis  Tumor grade
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