High telomerase reverse transcriptase (hTERT) messenger RNA level correlates with tumor recurrence in patients with favorable histology Wilms' tumor.
High telomerase reverse transcriptase (hTERT) messenger RNA level correlates with tumor recurrence in patients with favorable histology Wilms' tumor.
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发表时间：
1999-09
期刊：
影响因子：
11.2
通讯作者：
J. Dome;Seung Chung;T. Bergemann;C. Umbricht;M. Saji;L. Carey;L. Carey;P. Grundy;E. Perlman;N. Breslow;S. Sukumar
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作者：
J. Dome;Seung Chung;T. Bergemann;C. Umbricht;M. Saji;L. Carey;L. Carey;P. Grundy;E. Perlman;N. Breslow;S. Sukumar
端粒酶是一种逆转录酶，可维持染色体末端，补偿复制过程中发生的 DNA 逐渐丢失。高端粒酶活性对于几种类型的癌症来说是不利的预后特征。我们研究了端粒酶水平是否可以预测儿童肾恶性肿瘤肾母细胞瘤患者的预后。在一项针对 78 名组织学良好的肾母细胞瘤患者的病例队列研究中，我们比较了最终复发和未复发患者的肿瘤端粒酶水平。使用三种端粒酶测量方法：(a)端粒酶活性； (b) hTR（端粒酶的 RNA 成分）的表达； (c) hTERT（编码酶催化成分的基因）的 mRNA 表达。在可评估的样本中，81% 具有可检测的端粒酶活性，97% 具有可检测的 hTERT 转录物，100% 具有可检测的 hTR。端粒酶活性与 hTR 水平之间（r = 0.34，P = 0.02）以及端粒酶活性与 hTERT mRNA 水平之间（r = 0.32，P = 0.04）之间观察到弱相关性。在评估的变量中，只有 hTERT mRNA 表达与结果相关。复发肿瘤中的中位 hTERT mRNA 水平高于未复发肿瘤（1.42 vs 0.97 单位，P = 0.023，Wilcoxon）。 hTERT mRNA 水平作为连续变量的单变量分析表明，hTERT mRNA 水平每增加一个单位，复发风险 (RR) 就会增加 1.66 倍 [95% 置信区间 (CI)，1.2-2.3；95% 置信区间 (CI)，1.2-2.3； P 2 单位的 RR 为 6.40（95% CI，1.49-27.67，P = 0.013）。 hTERT mRNA 水平作为复发预测因子的多变量分析，根据肿瘤分期和诊断时年龄进行调整，显示 RR 为 1.48（95% CI，0.9-2.6；P = 0.16）。因此，hTERT mRNA 水平的测量可以使临床医生识别复发高风险的患者群体，并相应地调整他们的治疗。需要进行更大规模的研究来确定 hTERT 表达是否是一个独立的预后指标。需要进一步的生物学研究来辨别高 hTERT 表达与不良预后之间的联系是因果关系还是相关关系。
Telomerase is a reverse transcriptase that maintains chromosome ends, compensating for the progressive loss of DNA that occurs during replication. High telomerase enzyme activity is an unfavorable prognostic feature for several types of cancers. We investigated whether telomerase level predicts outcome for patients with the pediatric renal malignancy Wilms' tumor. In a case-cohort study of 78 patients with favorable histology Wilms' tumor, we compared tumor telomerase levels in patients with and without eventual recurrence. Three measures of telomerase were used: (a) telomerase enzyme activity; (b) expression of hTR, the RNA component of telomerase; and (c) mRNA expression of hTERT, the gene that encodes the catalytic component of the enzyme. Of the evaluable samples, 81% had detectable telomerase activity, 97% had detectable hTERT transcript, and 100% had detectable hTR. Weak correlations were observed between telomerase activity and hTR level (r = 0.34, P = 0.02) and between telomerase activity and hTERT mRNA level (r = 0.32, P = 0.04). Of the variables assessed, only hTERT mRNA expression correlated with outcome. The median hTERT mRNA level in tumors with recurrence was higher than that in tumors without recurrence (1.42 versus 0.97 units, P = 0.023, Wilcoxon). Univariate analysis of hTERT mRNA level as a continuous variable suggested that each unit increase in hTERT mRNA level increased the risk of recurrence (RR) by a factor of 1.66 [95% confidence interval (CI), 1.2-2.3; P 2 units had a RR of 6.40 (95% CI, 1.49-27.67, P = 0.013). Multivariate analysis of hTERT mRNA level as a predictor of recurrence, adjusted for tumor stage and age at diagnosis, revealed a RR of 1.48 (95% CI, 0.9-2.6; P = 0.16). Measurement of hTERT mRNA level may, therefore, enable clinicians to identify a population of patients at high risk for recurrence and to adjust their therapy accordingly. A larger study will be necessary to determine whether hTERT expression is an independent prognostic indicator. Further biological investigation is warranted to discern whether the link between high hTERT expression and unfavorable prognosis is causative or correlative.