Ozden Sevgi, Tiber Pinar Mega, Ozgen Zerrin, Ozyurt Hazan, Serakinci Nedime, Orun Oya
Clinic of Radiation Oncology, Dr. Lutfi Kirdar Kartal Training and Research Hospital, Semsi Denizer Street, Istanbul, 34890, Turkey.
Biophysics Department, Marmara University School of Medicine, Maltepe Basibuyuk Yolu Street, Istanbul, 34854, Turkey.
Biol Res. 2014 Nov 25;47(1):61. doi: 10.1186/0717-6287-47-61.
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.
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).
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.
端粒是由特定串联重复序列（5'-TTAGGG-3'）组成的保护帽。每次细胞分裂时端粒的缩短被称为细胞的“有丝分裂时钟”，这使得端粒成为寿命的重要调节因子。TRF2是端粒保护蛋白复合体的关键成员之一，该复合体是一种负责维持帽结构的蛋白质复合体，TRF2的缺失或突变会导致DNA损伤、衰老或凋亡。由于癌症常与异常的细胞周期进程、有缺陷的DNA修复或凋亡途径相关，TRF2可能是癌症治疗的一个潜在候选靶点。在此，我们研究了TRF2水平在宫颈癌患者中的预后作用。通过实时PCR分析后，以中位数为参照评估倍数诱导率。使用Kaplan-Meier长秩检验计算总生存率、无远处疾病生存率和无局部复发生存率。
与低表达患者相比，TRF2高表达患者的五年总生存率和无病生存率均更长，但结果无统计学意义（分别为69.2%和28.9%）。高表达和低表达患者的平均无局部复发生存率（LRF）非常接近（分别为58.6，CI：44.3 - 72.9个月和54.5，CI：32.1 - 76.9个月）。五年期末LRF的累积比例，TRF2高表达为76.9%，低表达为57.1%（P = 0.75）。生存率与Bcl-xL和p53基因表达之间存在统计学显著差异，但与TRF2无关。TRF2表达与凋亡以及远处转移之间存在显著相关性（分别为P = 0.045和0.036）。此外，TRF2高表达水平对IIIB-IVA期患者的五年生存率有积极影响（P = 0.04）。
我们的结果支持TRF2在凋亡中的作用，并暗示其与晚期患者的远处转移和生存呈正相关。不同TRF2表达患者生存期的显著差异表明，TRF2可能是评估宫颈癌生存的一个候选因素，这一初步观察结果应通过更大规模的队列进一步验证。
