Abstract
BackgroundBesides being one of the most prevalent cancers among women, incidence and mortality rates of endometrial cancer (EC) are still increasing. The E2F family of transcriptional factors is involved in cell differentiation, apoptosis, and inhibition of DNA damage response, thus affecting growth and invasion of tumor cells.MethodsWe used multiple bioinformatics tools to explore the role of E2F family in endometrial cancer.ResultsThe expression of E2F1/2/3/7/8 was significantly upregulated in endometrial cancer tissues, converse to E2F4, which was downregulated. Methylation downregulates all E2Fs except for E2F2. Accordingly, E2F1/2/3/5/7/8 are potential diagnostic biomarkers for EC. In particular, EC patients displaying upregulated E2F1, and E2F3 expression had a worse overall survival and relapse-free survival. E2F8, E2F7, and E2F1 were the top three, most-frequently altered genes in endometrial cancer. E2F family activates apoptosis pathways, regulates cell cycle, and impairs DNA damage response pathways. Drug-sensitivity analysis demonstrated that the level of E2F2/3/8 negatively correlated with drug resistance. Meanwhile, immune infiltrations analysis revealed that E2F family is associated with recruitment of several immune cells. Enrichment analysis on its part revealed that the E2F family is mainly associated with cell cycle, sequence-specific DNA binding, nuclear transcription factor complex, PI3K-Akt signaling, and p53 signaling pathway. We also identified multiple E2Fs-associated miRNA and kinase targets in endometrial cancer.ConclusionOur study revealed the unique expression signature and clinical significance of E2F family in EC, demonstrating the potential clinical utility of these transcription factors (TF) in endometrial cancer.
Highlights
Endometrial cancer (EC) is one of the most prevalent cancers among women
Our analysis revealed significant over-expression of E2F1 (Figure 1A, P < 1E-12), E2F2 (Figure 1B, P = 1.62E12), E2F3 (Figure 1C, P = 1.62E-12), E2F5 (Figure 1E, P = 3.0E-15), E2F7 (Figure 1G, P = 1.62E-12), and E2F8 (Figure 1H, P = 1.62E-12) in UCEC tissues, converse to E2F4 (Figure 1D, P = 2.02E-12), which was downregulated in the same tissues
We suggested that the expression of E2F1/2/3/7/8 was significantly upregulated in EC tissues, converse to E2F4, which was downregulated
Summary
Endometrial cancer (EC) is one of the most prevalent cancers among women. It is estimated that in US alone, 65,620 women will be diagnosed with EC, of which 12,590 of them will die of this disease in 2020 (Siegel et al, 2020). These bleak statistics notwithstanding, the incidence and mortality rate due to EC are all increasing. Besides being one of the most prevalent cancers among women, incidence and mortality rates of endometrial cancer (EC) are still increasing. The E2F family of transcriptional factors is involved in cell differentiation, apoptosis, and inhibition of DNA damage response, affecting growth and invasion of tumor cells
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