Prediction of survival in stage I lung carcinoma patients by telomerase function evaluation

Prediction of survival in stage I lung carcinoma patients by telomerase function evaluation
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DOI:
10.1097/01.lab.0000017165.26718.60
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发表时间:
2002-06-01
影响因子:
5
通讯作者:
Bosari, S
Bosari, S
中科院分区:
医学2区
文献类型:
--
作者:
Marchetti, A;Pellegrini, C;Bosari, S

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端粒酶活性和端粒酶逆转录酶(hTERT)表达在人类恶性肿瘤中升高。我们研究了端粒重复序列扩增法(TRAP)测定的端粒酶活性和实时RT-PCR检测的hTERT水平在I期非小细胞肺癌。本研究的目的是比较这两种技术在端粒酶功能检测中的作用,并评价其预后意义。分别采用TRAP法和实时RT-PCR法检测90例I期非小细胞肺癌患者的端粒酶活性和hTERT水平。通过卡方检验和Fisher精确检验分析变量。采用Kaplan-Meier法分析生存率。采用考克斯比例风险模型进行多变量分析。60例(67%)癌组织端粒酶活性增高。hTERT在43例(48%)癌中升高。仅21例(23%)肿瘤的TRAP和hTERT表达水平均为低端粒酶功能。端粒酶活性和hTERT显着相关(p = 0.017),虽然35例显示不一致的结果。端粒酶活性和hTERT水平与患者总体生存率和无病生存率均显著相关(TRAP分别为p = 0.019和p = 0.018,hTERT分别为p = 0.011和p = 0.012)。在21例显示低端粒酶功能的肿瘤患者中,由TRAP和hTERT表达水平定义,只有1例死于该疾病(p = 0.0053)。我们的研究结果表明,在这项研究中使用的两种技术评估端粒酶功能的单独方面和他们的组合提供了强大的肺癌患者的预后信息。
Telomerase activity and telomerase reverse transcriptase (hTERT) expression are elevated in human malignancies. We have investigated telomerase activity measured by the telomeric repeat amplification protocol (TRAP) assay and hTERT levels by real-time RT-PCR in stage I non-small-cell lung carcinomas. The purposes of our study included the comparison of these two techniques in the assessment of telomerase function and the evaluation of their prognostic significance. Telomerase activity and hTERT levels were determined in 90 stage I non-small-cell lung carcinoma patients, using TRAP assay and real-time RT-PCR, respectively. Variables were analyzed by the chi(2) and Fisher exact tests. Survival was analyzed by the Kaplan-Meier method. Multivariate analysis was performed with the Cox's proportional hazards model. Telomerase activity was elevated in 60 (67%) carcinomas. hTERT was elevated in 43 (48%) carcinomas. Only 21 (23%) tumors had low telomerase function by both TRAP and hTERT expression levels. Telomerase activity and hTERT were significantly correlated (p = 0.017), although 35 cases displayed discordant results. Both telomerase activity and hTERT levels were significantly associated with poor patient overall and disease-free survival (p = 0.019 and p = 0.018 for TRAP, and p = 0.011 and p = 0.012 for hTERT, respectively). Among the 21 patients with tumors displaying low telomerase function, defined by both TRAP and hTERT expression levels, only one succumbed to the disease (p = 0.0053). Our results suggest that the two techniques used in this study evaluate separate aspects of telomerase function and their combination provides powerful prognostic information in lung cancer patients.