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Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients

BACKGROUND: Telomeres are protective caps consisted of specific tandem repeats (5′-TTAGGG-3′). Shortening of telomeres at each cell division is known as “mitotic clock” of the cells, which renders telomeres as important regulators of lifespan. TRF2 is one of the critical members of shelterin complex...

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Autores principales: Ozden, Sevgi, Tiber, Pinar Mega, Ozgen, Zerrin, Ozyurt, Hazan, Serakinci, Nedime, Orun, Oya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335779/
https://www.ncbi.nlm.nih.gov/pubmed/25654471
http://dx.doi.org/10.1186/0717-6287-47-61
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author Ozden, Sevgi
Tiber, Pinar Mega
Ozgen, Zerrin
Ozyurt, Hazan
Serakinci, Nedime
Orun, Oya
author_facet Ozden, Sevgi
Tiber, Pinar Mega
Ozgen, Zerrin
Ozyurt, Hazan
Serakinci, Nedime
Orun, Oya
author_sort Ozden, Sevgi
collection PubMed
description BACKGROUND: Telomeres are protective caps consisted of specific tandem repeats (5′-TTAGGG-3′). Shortening of telomeres at each cell division is known as “mitotic clock” of the cells, which renders telomeres as important regulators of lifespan. TRF2 is one of the critical members of shelterin complex, which is a protein complex responsible from the preservation of cap structure, and loss or mutation of TRF2 results in DNA damage, senescence or apoptosis. Since cancer is frequently associated with aberrant cell cycle progression, defective DNA repair or apoptosis pathways, TRF2 could be one likely candidate for cancer therapy. Here we investigated the prognostic role of TRF2 levels in cervical cancer patients. Fold-induction rates were evaluated with respect to median values after real-time PCR analysis. Overall survival, distant disease-free and local recurrence-free survival rates were calculated using Kaplan-Meier long rank test. RESULTS: Both five year overall- and disease-free survival rates were longer in patients with higher TRF2 expression compared to lower expression, but results were not statistically significant (69.2% vs 28.9%, respectively). Mean local recurrence-free survivals (LRF) were very close ( 58.6, CI: 44.3-72.9 vs 54.5, CI: 32.1-76.9 months) for high and low expressions, respectively. Cumulative proportion of LRF at the end of five year period was 76.9% for high and 57.1% for low TRF2 expression (P = 0.75). Statistically significant difference was found between survival ratios and Bcl-xL and p53 gene expressions, but not with TRF2. A respectable correlation between TRF2 expression and apoptosis along with distant metastasis was noted (P = 0.045 and 0.036, respectively). Additionally, high TRF2 expression levels had a positive impact in five year survival rate of stage IIIB-IVA patients (P = 0.04). CONCLUSIONS: Our results support the role of TRF2 in apoptosis and imply a positive relation with distant metastases and survival in advanced stage patients. The remarkable difference in survival periods of patients with different TRF2 expressions suggest that TRF2 may be a candidate factor to estimate survival for cervical cancer, a preliminary observation which should further be verified with a larger cohort.
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spelling pubmed-43357792015-02-21 Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients Ozden, Sevgi Tiber, Pinar Mega Ozgen, Zerrin Ozyurt, Hazan Serakinci, Nedime Orun, Oya Biol Res Research Article BACKGROUND: Telomeres are protective caps consisted of specific tandem repeats (5′-TTAGGG-3′). Shortening of telomeres at each cell division is known as “mitotic clock” of the cells, which renders telomeres as important regulators of lifespan. TRF2 is one of the critical members of shelterin complex, which is a protein complex responsible from the preservation of cap structure, and loss or mutation of TRF2 results in DNA damage, senescence or apoptosis. Since cancer is frequently associated with aberrant cell cycle progression, defective DNA repair or apoptosis pathways, TRF2 could be one likely candidate for cancer therapy. Here we investigated the prognostic role of TRF2 levels in cervical cancer patients. Fold-induction rates were evaluated with respect to median values after real-time PCR analysis. Overall survival, distant disease-free and local recurrence-free survival rates were calculated using Kaplan-Meier long rank test. RESULTS: Both five year overall- and disease-free survival rates were longer in patients with higher TRF2 expression compared to lower expression, but results were not statistically significant (69.2% vs 28.9%, respectively). Mean local recurrence-free survivals (LRF) were very close ( 58.6, CI: 44.3-72.9 vs 54.5, CI: 32.1-76.9 months) for high and low expressions, respectively. Cumulative proportion of LRF at the end of five year period was 76.9% for high and 57.1% for low TRF2 expression (P = 0.75). Statistically significant difference was found between survival ratios and Bcl-xL and p53 gene expressions, but not with TRF2. A respectable correlation between TRF2 expression and apoptosis along with distant metastasis was noted (P = 0.045 and 0.036, respectively). Additionally, high TRF2 expression levels had a positive impact in five year survival rate of stage IIIB-IVA patients (P = 0.04). CONCLUSIONS: Our results support the role of TRF2 in apoptosis and imply a positive relation with distant metastases and survival in advanced stage patients. The remarkable difference in survival periods of patients with different TRF2 expressions suggest that TRF2 may be a candidate factor to estimate survival for cervical cancer, a preliminary observation which should further be verified with a larger cohort. BioMed Central 2014-11-25 /pmc/articles/PMC4335779/ /pubmed/25654471 http://dx.doi.org/10.1186/0717-6287-47-61 Text en © Ozden et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Ozden, Sevgi
Tiber, Pinar Mega
Ozgen, Zerrin
Ozyurt, Hazan
Serakinci, Nedime
Orun, Oya
Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients
title Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients
title_full Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients
title_fullStr Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients
title_full_unstemmed Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients
title_short Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients
title_sort expression of trf2 and its prognostic relevance in advanced stage cervical cancer patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4335779/
https://www.ncbi.nlm.nih.gov/pubmed/25654471
http://dx.doi.org/10.1186/0717-6287-47-61
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