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Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival

Risk of relapse of endometrial cancer (EC) after surgical treatment is 13% and recurrent disease carries a poor prognosis. Research into prognostic indicators is essential to improve EC management and outcome. “Immortality” of most cancer cells is dependent on telomerase, but the role of associated...

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Autores principales: Button, Lucy, Rogers, Bryony, Thomas, Emily, Bradfield, Alice, Alnafakh, Rafah, Drury, Josephine, Hapangama, Dharani K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775816/
https://www.ncbi.nlm.nih.gov/pubmed/35054812
http://dx.doi.org/10.3390/ijms23020626
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author Button, Lucy
Rogers, Bryony
Thomas, Emily
Bradfield, Alice
Alnafakh, Rafah
Drury, Josephine
Hapangama, Dharani K.
author_facet Button, Lucy
Rogers, Bryony
Thomas, Emily
Bradfield, Alice
Alnafakh, Rafah
Drury, Josephine
Hapangama, Dharani K.
author_sort Button, Lucy
collection PubMed
description Risk of relapse of endometrial cancer (EC) after surgical treatment is 13% and recurrent disease carries a poor prognosis. Research into prognostic indicators is essential to improve EC management and outcome. “Immortality” of most cancer cells is dependent on telomerase, but the role of associated proteins in the endometrium is poorly understood. The Cancer Genome Atlas data highlighted telomere/telomerase associated genes (TTAGs) with prognostic relevance in the endometrium, and a recent in silico study identified a group of TTAGs and proteins as key regulators within a network of dysregulated genes in EC. We characterise relevant telomere/telomerase associated proteins (TTAPs) NOP10, NHP2, NOP56, TERF1, TERF2 and TERF2IP in the endometrium using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). qPCR data demonstrated altered expression of multiple TTAPs; specifically, increased NOP10 (p = 0.03) and reduced NHP2 (p = 0.01), TERF2 (p = 0.01) and TERF2IP (p < 0.003) in EC relative to post-menopausal endometrium. Notably, we report reduced NHP2 in EC compared to post-menopausal endometrium in qPCR and IHC (p = 0.0001) data; with survival analysis indicating high immunoscore is favourable in EC (p = 0.0006). Our findings indicate a potential prognostic role for TTAPs in EC, particularly NHP2. Further evaluation of the prognostic and functional role of the examined TTAPs is warranted to develop novel treatment strategies.
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spelling pubmed-87758162022-01-21 Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival Button, Lucy Rogers, Bryony Thomas, Emily Bradfield, Alice Alnafakh, Rafah Drury, Josephine Hapangama, Dharani K. Int J Mol Sci Article Risk of relapse of endometrial cancer (EC) after surgical treatment is 13% and recurrent disease carries a poor prognosis. Research into prognostic indicators is essential to improve EC management and outcome. “Immortality” of most cancer cells is dependent on telomerase, but the role of associated proteins in the endometrium is poorly understood. The Cancer Genome Atlas data highlighted telomere/telomerase associated genes (TTAGs) with prognostic relevance in the endometrium, and a recent in silico study identified a group of TTAGs and proteins as key regulators within a network of dysregulated genes in EC. We characterise relevant telomere/telomerase associated proteins (TTAPs) NOP10, NHP2, NOP56, TERF1, TERF2 and TERF2IP in the endometrium using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). qPCR data demonstrated altered expression of multiple TTAPs; specifically, increased NOP10 (p = 0.03) and reduced NHP2 (p = 0.01), TERF2 (p = 0.01) and TERF2IP (p < 0.003) in EC relative to post-menopausal endometrium. Notably, we report reduced NHP2 in EC compared to post-menopausal endometrium in qPCR and IHC (p = 0.0001) data; with survival analysis indicating high immunoscore is favourable in EC (p = 0.0006). Our findings indicate a potential prognostic role for TTAPs in EC, particularly NHP2. Further evaluation of the prognostic and functional role of the examined TTAPs is warranted to develop novel treatment strategies. MDPI 2022-01-06 /pmc/articles/PMC8775816/ /pubmed/35054812 http://dx.doi.org/10.3390/ijms23020626 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Button, Lucy
Rogers, Bryony
Thomas, Emily
Bradfield, Alice
Alnafakh, Rafah
Drury, Josephine
Hapangama, Dharani K.
Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival
title Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival
title_full Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival
title_fullStr Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival
title_full_unstemmed Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival
title_short Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival
title_sort telomere and telomerase-associated proteins in endometrial carcinogenesis and cancer-associated survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775816/
https://www.ncbi.nlm.nih.gov/pubmed/35054812
http://dx.doi.org/10.3390/ijms23020626
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