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...

Full description

Bibliographic Details
Main Authors: Alice Bradfield, Lucy Button, Josephine Drury, Daniel C. Green, Christopher J. Hill, Dharani K. Hapangama
Format: Article
Language:English
Published: MDPI AG 2020-09-01
Series:Methods and Protocols
Subjects:
Online Access:https://www.mdpi.com/2409-9279/3/3/63
_version_ 1797554723801268224
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.
first_indexed 2024-03-10T16:36:06Z
format Article
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
record_format Article
series Methods and Protocols
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
work_keys_str_mv AT alicebradfield investigatingtheroleoftelomereandtelomeraseassociatedgenesandproteinsinendometrialcancer
AT lucybutton investigatingtheroleoftelomereandtelomeraseassociatedgenesandproteinsinendometrialcancer
AT josephinedrury investigatingtheroleoftelomereandtelomeraseassociatedgenesandproteinsinendometrialcancer
AT danielcgreen investigatingtheroleoftelomereandtelomeraseassociatedgenesandproteinsinendometrialcancer
AT christopherjhill investigatingtheroleoftelomereandtelomeraseassociatedgenesandproteinsinendometrialcancer
AT dharanikhapangama investigatingtheroleoftelomereandtelomeraseassociatedgenesandproteinsinendometrialcancer