Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer
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 telomera...
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MDPI AG
2020-09-01
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Series: | Methods and Protocols |
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Online Access: | https://www.mdpi.com/2409-9279/3/3/63 |
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author | Alice Bradfield Lucy Button Josephine Drury Daniel C. Green Christopher J. Hill Dharani K. Hapangama |
author_facet | Alice Bradfield Lucy Button Josephine Drury Daniel C. Green Christopher J. Hill Dharani K. Hapangama |
author_sort | Alice Bradfield |
collection | DOAJ |
description | 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 <i>NOP56</i>, <i>WFS1</i>, <i>ANAPC4</i> and <i>TUBB4A</i>. Probing the prognostic and therapeutic utility of these novel TTAGP markers will form an exciting basis for future research. |
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id | doaj.art-9e0a0c3f3e454109954138afaa191764 |
institution | Directory Open Access Journal |
issn | 2409-9279 |
language | English |
last_indexed | 2024-03-10T16:36:06Z |
publishDate | 2020-09-01 |
publisher | MDPI AG |
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spelling | doaj.art-9e0a0c3f3e454109954138afaa1917642023-11-20T12:28:38ZengMDPI AGMethods and Protocols2409-92792020-09-01336310.3390/mps3030063Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial CancerAlice Bradfield0Lucy Button1Josephine Drury2Daniel C. Green3Christopher J. Hill4Dharani K. Hapangama5Department of Women’s and Children’s Health, University of Liverpool, Crown St, Liverpool L69 7ZX, UKFaculty of Health and Life Sciences, University of Liverpool, Brownlow Hill, Liverpool L69 7ZX, UKDepartment of Women’s and Children’s Health, University of Liverpool, Crown St, Liverpool L69 7ZX, UKInstitute of Life Course and Medical Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L7 8TX, UKDepartment of Women’s and Children’s Health, University of Liverpool, Crown St, Liverpool L69 7ZX, UKDepartment of Women’s and Children’s Health, University of Liverpool, Crown St, Liverpool L69 7ZX, UKEndometrial 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 <i>NOP56</i>, <i>WFS1</i>, <i>ANAPC4</i> and <i>TUBB4A</i>. Probing the prognostic and therapeutic utility of these novel TTAGP markers will form an exciting basis for future research.https://www.mdpi.com/2409-9279/3/3/63telomeretelomeraseendometrial cancerprognosisbioinformatics analysistranscriptome |
spellingShingle | Alice Bradfield Lucy Button Josephine Drury Daniel C. Green Christopher J. Hill Dharani K. Hapangama Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer Methods and Protocols telomere telomerase endometrial cancer prognosis bioinformatics analysis transcriptome |
title | Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer |
title_full | Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer |
title_fullStr | Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer |
title_full_unstemmed | Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer |
title_short | Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer |
title_sort | investigating the role of telomere and telomerase associated genes and proteins in endometrial cancer |
topic | telomere telomerase endometrial cancer prognosis bioinformatics analysis transcriptome |
url | https://www.mdpi.com/2409-9279/3/3/63 |
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