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

Abstract

BackgroundTelomeres 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.ResultsBoth 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).ConclusionsOur 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.

Revisiting Telomere Shortening in Cancer

“…We also should mention the expression levels of shelterin proteins in cancer. Previous clinical studies have reported that expression levels of shelterin genes, such as TRF1, TRF2, TIN2, and, in some cases, POT1, are elevated in many types of cancer as compared to the noncancerous tissues [98,99]. Also, it has been reported that TRF1, TRF2 and TIN2 expression levels are correlated with the progression level of cancers [100,101,102].…”

Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis

“…Early diagnosis and treatment represent the key to increasing cervical cancer survival rates and improving quality of life in patients. Investigations have focused on the mechanisms associated with cervical cancer invasion and metastasis, which are important for the improvement of patient prognoses (Ozden et al, 2014;Winer et al, 2015) Tumorigenesis is associated with multiple genes and the interaction between several factors. The pathological process of cervical cancer is related to apoptosis suppression, which is regulated by tumor-suppressor gene inactivation, oncogene activation or mutation, and anti-apoptosis gene overexpression (Ouyang et al, 2008a,b).…”

A Novel DNA Replication-Related Signature Predicting Recurrence After R0 Resection of Pancreatic Ductal Adenocarcinoma: Prognostic Value and Clinical Implications

“…TERF2 has remarkable tumor-specific effects; however, its role in PDAC remains unknown. TERF2 is a robust predictor of patient survival in cervical cancer ( Benhamou et al, 2016 ) and oral carcinoma ( Ozden et al, 2014 ). The role of TERF2 in cancers is primarily to promote angiogenesis ( El Maï et al, 2014 ; Zizza et al, 2019 ).…”