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端粒酶活性作为I期非小细胞肺癌的预后指标

Telomerase activity as a prognostic indicator in stage I non-small cell lung cancer.

作者信息

Marchetti A, Bertacca G, Buttitta F, Chella A, Quattrocolo G, Angeletti C A, Bevilacqua G

机构信息

Department of Oncology and Neurosciences, University Gabriele D'Annunzio, Chieti, Italy.

出版信息

Clin Cancer Res. 1999 Aug;5(8):2077-81.

Abstract

Patients with stage I non-small cell lung cancer (NSCLC) are typically treated with surgical resection alone. However, about one-third of such patients develop disease recurrence and die within 5 years after complete resection. The ability to predict recurrence could represent an important contribution to treatment planning. This study evaluates the presence of telomerase activity in tumor cells as a predictor of disease recurrence and cancer-related death after operation for stage I NSCLC patients. The activity of the telomerase enzyme was investigated by telomeric repeat amplification protocol (TRAP) in tumors and matching normal lung tissue samples obtained from 107 consecutive operable patients with pathological stage I NSCLC. Telomerase activity was detected in 66 (62%) of the 107 tumors examined and in none of the corresponding adjacent noncancerous lung tissue samples. Correlation with pathological parameters showed that telomerase activity was associated with histopathological grade (P = 0.0135) but not with tumor size or histological type. Univariate survival curves, estimated using the method of Kaplan and Meier, defined a significant association between telomerase activity and both disease-free survival (P = 0.0115) and overall survival (P = 0.0129). In multivariate analyses, performed by Cox's proportional hazards regression models, the presence of telomerase activity was the only strong predictor of disease-free survival (P = 0.0173) and overall survival (P = 0.0187). Our data indicate that telomerase activity can be an important prognostic factor that should be considered in future prospective trials of adjuvant therapy for high-risk stage I NSCLC patients.

摘要

I期非小细胞肺癌(NSCLC)患者通常仅接受手术切除治疗。然而,约三分之一的此类患者会出现疾病复发,并在完全切除后的5年内死亡。预测复发的能力可能对治疗规划有重要贡献。本研究评估肿瘤细胞中端粒酶活性的存在,作为I期NSCLC患者术后疾病复发和癌症相关死亡的预测指标。通过端粒重复序列扩增法(TRAP),对从107例连续可手术的病理I期NSCLC患者获取的肿瘤及匹配的正常肺组织样本中的端粒酶活性进行了研究。在检测的107个肿瘤中,66个(62%)检测到端粒酶活性,而相应的相邻非癌肺组织样本中均未检测到。与病理参数的相关性显示,端粒酶活性与组织病理学分级相关(P = 0.0135),但与肿瘤大小或组织学类型无关。使用Kaplan-Meier方法估计的单变量生存曲线表明,端粒酶活性与无病生存期(P = 0.0115)和总生存期(P = 0.0129)均存在显著关联。在通过Cox比例风险回归模型进行的多变量分析中,端粒酶活性的存在是无病生存期(P = 0.0173)和总生存期(P = 0.0187)的唯一强预测指标。我们的数据表明,端粒酶活性可能是一个重要的预后因素,在未来针对高危I期NSCLC患者的辅助治疗前瞻性试验中应予以考虑。

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