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人胰腺腺癌中E2F转录因子的预后及免疫浸润综合分析

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

作者信息

Liu Xu-Sheng, Gao Yan, Liu Chao, Chen Xue-Qin, Zhou Lu-Meng, Yang Jian-Wei, Kui Xue-Yan, Pei Zhi-Jun

机构信息

Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

Medical Imaging Center, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

出版信息

Front Oncol. 2021 Feb 2;10:606735. doi: 10.3389/fonc.2020.606735. eCollection 2020.

DOI:10.3389/fonc.2020.606735
PMID:33604289
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7884810/
Abstract

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 up-regulated 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- 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.

摘要

背景

E2F转录因子（E2Fs）是一组在高等真核生物中编码转录因子家族的基因。它们参与多种细胞功能，并且在许多组织和器官中上调。然而，不同E2Fs在胰腺癌（PAAD）中的表达水平、基因变异、分子机制和生物学功能，以及其与PAAD患者预后和免疫浸润的关系尚未完全阐明。

方法

在本研究中，我们使用Oncomine、GEPIA、Kaplan Meier plotter、cBioPortal、GeneMANIA、STRING和Metascape数据库，研究了PAAD中E2Fs的mRNA表达水平、基因变异、预后价值和基因-基因相互作用网络。然后，使用TIMER数据库研究E2Fs表达与肿瘤免疫侵袭之间的关系。最后，我们通过免疫组化（IHC）证实了PAAD中E2Fs的表达。

结果

E2F1/3/5/8的转录水平在PAAD中明显上调，E2F2/3/6/8的高表达明显与PAAD患者的肿瘤分期相关。PAAD患者中E2F1/2/3/4/5/7/8的异常表达与PAAD患者的临床结局相关。我们还发现，与相邻正常组织相比，PAAD组织中E2F1/3/5/8的表达水平更高。E2Fs及其邻近基因的功能主要与RNA聚合酶II启动子的转录起始有关。E2Fs及其邻近蛋白的功能主要与细胞周期、病毒致癌作用、FoxO信号通路、TGF-β信号通路及癌症中的转录紊乱和Wnt信号通路有关。我们还发现，E2Fs的表达与免疫浸润显著相关，包括B细胞、CD8 + T细胞、CD4 + T细胞、中性粒细胞、巨噬细胞和树突状细胞。

结论

我们的研究可能为PAAD患者免疫治疗靶点的选择和预后生物标志物提供新的见解。

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