E2F2 induces MCM4, CCNE2 and WHSC1 upregulation in ovarian cancer and predicts poor overall survival

L. Xie, T. Li, L.-H. Yang

Department of Gynecology, the First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. lhyangdc@hotmail.com

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• Oncology

OBJECTIVE: To explore the genes co-upregulated with E2F2 in ovarian cancer and their association with survival outcomes in ovarian cancer patients.

MATERIALS AND METHODS: The raw data of GDS3592 was downloaded from GEO datasets for reanalysis. The overlapping subset between the top 150 upregulated genes in ovarian cancer epithelial cells (CEPIs) and the E2F2 positively correlated genes (Pearson’s r≥0.5) in ovarian cancer cohort in TCGA was identified. The association between E2F2, MCM4, CCNE2 and WHSC1 and overall survival (OS) and recurrence-free survival (RFS) in ovarian cancer patients were assessed using Kaplan-Meier plotter.

RESULTS: E2F2 is a significantly upregulated transcription factor in CEPIs. MCM4, CCNE2, and WHSC1 are co-upregulated with E2F2 among the 308 ovarian cancer samples (Pearson’s r=0.5159, 0.3963 and 0.4941 respectively). Enforced E2F2 expression significantly enhanced MCM4, CCNE2 and WHSC1 transcription in SKOV3 and A2780 cells. High E2F2 and CCNE2 expression are associated with worse OS (high E2F2, HR: 1.48, 95%CI: 1.17-1.85, p<0.01; high CCNE2, HR: 1.36, 95%CI: 1.15-1.6, p<0.01). High MCM expression might be associated with worse RFS at the margin of significance (HR: 1.18, 95%CI: 1.00-1.39, p=0.055).

CONCLUSIONS: MCM4, CCNE2, and WHSC1 are co-upregulated with E2F2 in ovarian cancer. Enforced E2F2 expression significantly increased MCM4, CCNE2, and WHSC1 expression in ovarian cancer cells. High E2F2 and CCNE2 expression are associated with worse OS among ovarian cancer patients.

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