Comprehensive Analysis of Prognostic and Immune Infiltrates for E2F Transcription Factors in Human Pancreatic Adenocarcinoma.

Background: E2F transcription factors (E2Fs) are a group of genes encoding a family of transcription factors in higher eukaryotes. They are involved in a variety of cellular functions and are upregulated in many tissues and organs. However, the expression level, genetic variation, molecular mechanism and biological function of different E2Fs in PAAD and its relationship with the prognosis and immune infiltration in patients with PAAD have not been fully elucidated. Methods: In this study, we investigated the mRNA expression level, genetic variation, prognostic value and gene-gene interaction network of E2Fs in PAAD using the Oncomine, GEPIA, Kaplan Meier plotter, cBioPortal, GeneMANIA, STRING and Metascape database. Then, the relationship between E2Fs expression and tumor immune invasion was studied by using the TIMER database. Finally, we confirmed the expression of E2Fs in PAAD by IHC. Results: The transcription levels of E2F1/3/5/8 are obviously up-regulated in PAAD and the high expression of E2F2/3/6/8 was apparently associated with the tumor stage of patients with PAAD. The abnormal expression of E2F1/2/3/4/5/7/8 in PAAD patients is related to the clinical outcome of PAAD patients. We also found that PAAD tissues have higher expression levels of E2F1/3/5/8 compared with adjacent normal tissues. The function of E2Fs and its neighboring genes is mainly related to the transcription initiation of the RNA polymerase Ⅱ promoter. The functions of E2Fs and its neighboring proteins are mainly related to cell cycle, virus carcinogenesis, FoxO signaling pathway, TGF-β signaling pathway, transcriptional disorders in cancer and Wnt signaling pathway. We also found that the expression of E2Fs was significantly correlated with immune infiltrates, including B cells, CD8+ T cells, CD4+T cells, neutrophils, macrophages, and dendritic cells. Conclusions: Our study may provide new insights into the choice of immunotherapy targets and prognostic biomarkers in PAAD patients.