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探究端粒及端粒酶相关基因和蛋白质在子宫内膜癌中的作用。

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer.

作者信息

Bradfield Alice, Button Lucy, Drury Josephine, Green Daniel C, Hill Christopher J, Hapangama Dharani K

机构信息

Department of Women's and Children's Health, University of Liverpool, Crown St, Liverpool L69 7ZX, UK.

Faculty of Health and Life Sciences, University of Liverpool, Brownlow Hill, Liverpool L69 7ZX, UK.

出版信息

Methods Protoc. 2020 Sep 3;3(3):63. doi: 10.3390/mps3030063.

Abstract

Endometrial cancer (EC) is the commonest gynaecological malignancy. Current prognostic markers are inadequate to accurately predict patient survival, necessitating novel prognostic markers, to improve treatment strategies. Telomerase has a unique role within the endometrium, whilst aberrant telomerase activity is a hallmark of many cancers. The aim of the current in silico study is to investigate the role of telomere and telomerase associated genes and proteins (TTAGPs) in EC to identify potential prognostic markers and therapeutic targets. Analysis of RNA-seq data from The Cancer Genome Atlas identified differentially expressed genes (DEGs) in EC (568 TTAGPs out of 3467) and ascertained DEGs associated with histological subtypes, higher grade endometrioid tumours and late stage EC. Functional analysis demonstrated that DEGs were predominantly involved in cell cycle regulation, while the survival analysis identified 69 DEGs associated with prognosis. The protein-protein interaction network constructed facilitated the identification of hub genes, enriched transcription factor binding sites and drugs that may target the network. Thus, our in silico methods distinguished many critical genes associated with telomere maintenance that were previously unknown to contribute to EC carcinogenesis and prognosis, including , , and . Probing the prognostic and therapeutic utility of these novel TTAGP markers will form an exciting basis for future research.

摘要

子宫内膜癌(EC)是最常见的妇科恶性肿瘤。目前的预后标志物不足以准确预测患者的生存率,因此需要新的预后标志物来改善治疗策略。端粒酶在子宫内膜中具有独特作用,而异常的端粒酶活性是许多癌症的一个标志。当前这项计算机模拟研究的目的是调查端粒和端粒酶相关基因及蛋白(TTAGPs)在子宫内膜癌中的作用,以识别潜在的预后标志物和治疗靶点。对来自癌症基因组图谱的RNA测序数据进行分析,确定了子宫内膜癌中差异表达基因(DEGs)(3467个中有568个TTAGPs),并确定了与组织学亚型、高级别子宫内膜样肿瘤和晚期子宫内膜癌相关的DEGs。功能分析表明,DEGs主要参与细胞周期调控,而生存分析确定了69个与预后相关的DEGs。构建的蛋白质-蛋白质相互作用网络有助于识别枢纽基因、富集的转录因子结合位点以及可能靶向该网络的药物。因此,我们的计算机模拟方法识别出了许多与端粒维持相关的关键基因,这些基因以前未知对子宫内膜癌的发生和预后有影响,包括 、 、 和 。探究这些新型TTAGP标志物的预后和治疗效用将为未来的研究奠定令人兴奋的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de88/7565490/7c246b122225/mps-03-00063-g001.jpg

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