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 critica...

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Autores principales:	Ozden,Sevgi, Tiber,Pinar Mega, Ozgen,Zerrin, Ozyurt,Hazan, Serakinci,Nedime, Orun,Oya
Lenguaje:	English
Publicado:	Sociedad de Biología de Chile 2014
Materias:	Cervical cancer Radiotherapy Telomere repeat-binding factors 2 B-cell lymphoma-extra large Apoptosis
Acceso en línea:	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602014000100055
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spelling	oai:scielo:S0716-976020140001000552015-10-30Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patientsOzden,SevgiTiber,Pinar MegaOzgen,ZerrinOzyurt,HazanSerakinci,NedimeOrun,Oya Cervical cancer Radiotherapy Telomere repeat-binding factors 2 B-cell lymphoma-extra large Apoptosis 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.47 20142014-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602014000100055en10.1186/0717-6287-47-61
institution	Scielo Chile
collection	Scielo Chile
language	English
topic	Cervical cancer Radiotherapy Telomere repeat-binding factors 2 B-cell lymphoma-extra large Apoptosis
spellingShingle	Cervical cancer Radiotherapy Telomere repeat-binding factors 2 B-cell lymphoma-extra large Apoptosis 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
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.
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
title	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_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_sort	expression of trf2 and its prognostic relevance in advanced stage cervical cancer patients
publisher	Sociedad de Biología de Chile
publishDate	2014
url	http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602014000100055
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Expression of TRF2 and its prognostic relevance in advanced stage cervical cancer patients

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