Correlations of telomere length, telomerase activity, and telomeric-repeat binding factor 1 expression in colorectal carcinoma - Prognostic indications
Correlations of telomere length, telomerase activity, and telomeric-repeat binding factor 1 expression in colorectal carcinoma - Prognostic indications
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DOI：
10.1002/cncr.21625
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发表时间：
2006-02-01
期刊：
影响因子：
6.2
通讯作者：
Iniesta, P
中科院分区：
文献类型：
--
作者：
Garcia-Aranda, C;de Juan, C;Iniesta, P
背景端粒的维持被认为是肿瘤细胞永生化的重要步骤。本研究的目的是探讨端粒长度在结直肠癌（CRC）中的作用机制，并评估端粒状态对预后的影响。对91例结直肠癌患者手术切除的肿瘤组织进行了端粒功能相关因素的分析。作者研究了端粒酶活性、末端限制性片段（TRF）长度和端粒重复序列结合因子（TRF 1）表达，并分析了这些因素的预后意义。大多数肿瘤（81.3%）显示端粒酶活性。总体而言，CRC标本中的端粒明显短于正常相邻标本中的端粒（P = 0.02）。此外，显示端粒缩短的肿瘤比没有端粒缩短的肿瘤显示更高的TRF 1水平。在患者预后方面，在端粒较长的肿瘤患者组中观察到临床病程明显较差（P = 0.02），这一发现在考克斯比例风险模型中作为独立的预后因素出现（P = 0.04;相对风险6.48）。在端粒酶阳性的肿瘤患者中，端粒长度比（肿瘤组织与正常组织的比值）
BACKGROUND. Telomere maintenance has been proposed as an essential step for tumor cell immortalization. The objectives of the current study were to investigate the mechanisms implicated in telomere length in colorectal carcinoma (CRC) and to evaluate the prognostic impact of telomere status.METHODS. Ninety-one colorectal carcinoma samples that were obtained from patients who underwent surgery were analyzed to investigate the factors related to telomere function. The authors studied telomerase activity, terminal restriction fragment (TRF) length, and telomeric-repeat binding factor (TRF1) expression and analyzed the prognostic implications of those factors.RESULTS. Most tumors (81.3%) displayed telomerase activity. Overall, telomeres in CRC specimens were significantly shorter compared with telomeres in normal, adjacent specimens (P = 0.02). Moreover, tumors that demonstrated shortened telomeres displayed higher TRF1 levels than tumors without telomere shortening. In relation to patient prognosis, a significantly poor clinical course was observed in the group of patients who had tumors with longer telomeres (P = 0.02), and this finding emerged as an independent prognostic factor in a Cox proportional hazards model (P = 0.04; relative risk, 6.48). Among patients with tumors classified as telomerase-positive, telomere length ratios (the ratio of tumor tissues to normal tissues)