乳腺癌中端粒酶表达和端粒长度及其与辅助治疗和疾病结局的关系。
Telomerase expression and telomere length in breast cancer and their associations with adjuvant treatment and disease outcome.
机构信息
Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8034, USA.
出版信息
Breast Cancer Res. 2011 Jun 6;13(3):R56. doi: 10.1186/bcr2893.
INTRODUCTION
Telomere length plays important roles in maintaining genome stability and regulating cell replication and death. Telomerase has functions not only to extend telomere length but also to repair DNA damage. Studies have shown that telomerase may increase cancer cell resistance to DNA-damaging anticancer agents; tamoxifen may suppress telomerase expression in breast cancer cells. This study aimed to investigate the role of telomere length and telomerase activity in breast cancer prognosis.
METHODS
qPCR and qRT-PCR were used to analyze telomere length and telomerase expression, respectively, in tumor samples of 348 breast cancer patients. Cox regression analysis was performed to examine telomere length and telomerase expression in association with disease-free survival and cause-specific mortality.
RESULTS
Telomere length had no relation to tumor features or disease outcomes. Telomerase expression was detected in 53% of tumors. Larger tumors or aggressive disease were more likely to have telomerase expression. Among patients treated with chemotherapy, high telomerase was found to be associated with increased risk of death (hazard ratio (HR) = 3.15; 95% CI: 1.34 to 7.40) and disease recurrence (HR = 2.04; 95% CI: 0.96 to 4.30) regardless of patient age, disease stage, tumor grade, histological type or hormone receptor status. Patients treated with endocrine therapy had different results regarding telomerase: high telomerase appeared to be associated with better survival outcomes. Telomerase expression made no survival difference in patients who received both chemotherapy and endocrine therapy.
CONCLUSIONS
Overall, telomerase expression was not associated with disease outcome, but this finding may be masked by adjuvant treatment. Patients with high telomerase expression responded poorly to chemotherapy in terms of disease-free and overall survival, but fared better if treated with endocrine therapy.
简介
端粒长度在维持基因组稳定性和调节细胞复制和死亡方面发挥着重要作用。端粒酶不仅具有延长端粒长度的功能，而且还具有修复 DNA 损伤的功能。研究表明，端粒酶可能会增加癌细胞对 DNA 损伤型抗癌药物的耐药性；他莫昔芬可能会抑制乳腺癌细胞中端粒酶的表达。本研究旨在探讨端粒长度和端粒酶活性与乳腺癌预后的关系。
方法
使用 qPCR 和 qRT-PCR 分别分析 348 例乳腺癌患者肿瘤样本中的端粒长度和端粒酶表达。采用 Cox 回归分析端粒长度和端粒酶表达与无病生存和特定原因死亡率的关系。
结果
端粒长度与肿瘤特征或疾病结局无关。在 53%的肿瘤中检测到端粒酶表达。较大的肿瘤或侵袭性疾病更有可能表达端粒酶。在接受化疗的患者中，高端粒酶与死亡风险增加（风险比 (HR) = 3.15；95%CI：1.34 至 7.40）和疾病复发（HR = 2.04；95%CI：0.96 至 4.30）相关，无论患者年龄、疾病分期、肿瘤分级、组织学类型或激素受体状态如何。接受内分泌治疗的患者中端粒酶的结果不同：高端粒酶似乎与更好的生存结局相关。端粒酶表达在接受化疗和内分泌治疗的患者中对生存没有影响。
结论
总体而言，端粒酶表达与疾病结局无关，但这一发现可能被辅助治疗所掩盖。高端粒酶表达的患者在无病生存和总生存方面对化疗反应不佳，但如果接受内分泌治疗则预后较好。
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