Activation of signal transducer and activator of transcription-5 in prostate cancer predicts early recurrence
Activation of signal transducer and activator of transcription-5 in prostate cancer predicts early recurrence
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DOI：
10.1158/1078-0432.ccr-05-0562
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发表时间：
2005-08-15
影响因子：
11.5
通讯作者：
Nevalainen, MT
中科院分区：
文献类型：
--
作者：
Li, HZ;Zhang, Y;Nevalainen, MT
目的：我们之前已经证明，信号转导子和转录激活子 5 (Stat5) 是人类前列腺癌细胞的关键生存因子。此外，我们最近表明 Stat5 被高水平激活，特别是在高级别人类前列腺癌中。在这里，我们以疾病复发为终点，研究了前列腺癌中 Stat5 的激活是否与临床结果相关。实验设计：使用免疫组织化学在组织微阵列上检测 357 个石蜡包埋的前列腺癌标本中的活性核 Stat5 以及临床随访数据。通过单变量和多变量生存分析来分析前列腺癌标本中的 Stat5 激活状态，以确定 Stat5 的激活是否可以预测早期前列腺癌复发。对所有患者（无论格里森分级如何）以及中间格里森分级（3 和 4）的前列腺癌患者进行单独的统计分析。 结果和结论：前列腺癌中的 Stat5 激活与早期疾病复发相关（P=0.0399）。重要的是，活性 Stat5 还预测中等格里森级前列腺癌的无进展生存期较短 (P=0.0409)。在所有患者 (P=0.0565) 和格里森 3 级或 4 级患者 (P=0.0582) 中调整格里森分级、pT 分期、神经周围浸润或精囊浸润后，Stat5 激活仍然是独立的预后标志物。这项工作的结果也证实了我们之前的发现，即 Stat5 激活与前列腺癌的高组织学分级相关（R=0.11，P=0.033）。总之，我们的研究表明，活跃的 Stat5 可以区分出疾病可能进展较早的前列腺癌患者；因此，活性 Stat5 可能是选择更个体化治疗的有用标记。这项研究的结果需要在大型前瞻性队列中进行验证。
Purpose: We have shown previously that the signal transducer and activator of transcription-5 (Stat5) is a critical survival factor in human prostate cancer cells. In addition, we recently showed that Stat5 is activated at a high level, particularly in high-grade human prostate cancers. Here, we investigated whether activation of Stat5 in prostate cancer was linked to clinical outcome with disease recurrence as end point.Experimental Design: Immunohistochemistry was used to detect active, nuclear Stat5 in 357 paraffin-embedded prostate cancer specimens on a tissue microarray with clinical follow-up data. Stat5 activation status in prostate cancer specimens was analyzed by univariate and multivariate survival analysis to determine whether activation of Stat5 predicts earlier prostate cancer recurrence. Separate sets of statistical analysis were done for all patients regardless of Gleason grade and for patients with prostate cancer of intermediate Gleason grades (3 and 4).Results and Conclusions: Stat5 activation in prostate cancer was associated with early disease recurrence (P=0.0399). Importantly, active Stat5 also predicted shorter progression-free survival in intermediate Gleason grade prostate cancers (P=0.0409). Stat5 activation remained an independent prognostic marker after adjusting for Gleason grade, pT stage, perineural invasion, or seminal vesicle infiltration in all patients (P=0.0565) and in Gleason grade 3 or 4 patients (P=0.0582). The results of this work also confirmed our previous finding of association of Stat5 activation with a high histologic grade of prostate cancer (R=0.11, P=0.033). In summary, our study shows that active Stat5 distinguished prostate cancer patients whose disease is likely to progress earlier; therefore, active Stat5 may be a useful marker for selection of more individualized treatment. The results of this study need to be validated in a large prospective cohort.