High levels of phosphorylated form of Akt-1 in prostate cancer and non-neoplastic prostate tissues are strong predictors of biochemical recurrence
High levels of phosphorylated form of Akt-1 in prostate cancer and non-neoplastic prostate tissues are strong predictors of biochemical recurrence
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DOI：
10.1158/1078-0432.ccr-04-0477
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发表时间：
2004-10-01
影响因子：
11.5
通讯作者：
Harper, W
中科院分区：
文献类型：
--
作者：
Ayala, G;Thompson, T;Harper, W
Akt是一种丝氨酸-苏氨酸激酶，其在调节代谢、凋亡和增殖的几个方面的途径中磷酸化蛋白质。Akt信号传导促进增殖和增加细胞存活，并且被认为在前列腺癌进展中起重要作用。组织微阵列（640例患者）与三个核心的非肿瘤性前列腺，前列腺增生症，和指数肿瘤免疫染色抗体磷酸化Akt（Ser 473），数字化，并量化。表达指数（强度 * 百分比）用于统计分析。P-Akt-1染色在非肿瘤和癌组织中均发现，主要在细胞质位置。高水平的P-Akt-1几乎只在癌症中表达。Kaplan-Meier精算模型显示，P-Akt-1在前列腺癌中的高表达在单因素和多因素分析中均预示着较高的复发概率。Akt-1表达是一个独立的生化无复发生存的预后指标时，格里森6和7例患者分别进行了分析。令人惊讶的是，在非肿瘤组织中P-Akt-1的高水平表达也是生化复发的独立预测因子。这表明，一些患者可能具有表达高水平P-Akt-1的固有倾向，因此具有不良预后。我们的结论是，P-Akt-1是最有可能参与前列腺癌的进展，是一个很好的生化复发的生物标志物。
Akt is a serine-threonine-kinase that phosphorylates proteins in several pathways regulating aspects of metabolism, apoptosis, and proliferation. Akt signaling promotes proliferation and increased cell survival and is thought to play an important role in prostate cancer progression. Tissue microarrays (640 patients) with triplicate cores of nonneoplastic prostate, BPH, and index tumor were immunostained with antibody to Phospho-Akt (Ser473), digitized, and quantified. The expression index (Intensity*Percentage) was used for statistical analysis. P-Akt-1 staining was found in both the non-neoplastic and cancer tissues, predominantly in cytoplasmic locations. High level P-Akt-1 is expressed almost exclusively in cancer. By Kaplan-Meier actuarial model, high expression of P-Akt-1 in prostate cancer was predictive of a higher probability of recurrence on univariate and multivariate analysis. Akt-1 expression was an independent prognostic indicator of biochemical recurrence-free survival when Gleason 6 and 7 patients were analyzed separately. Surprisingly, a high level of P-Akt-1 expression in non-neoplastic tissues is also an independent predictor of biochemical recurrence. This suggests that some patients might have an inherent predisposition to express a high level of P-Akt-1 and, therefore, to have an adverse prognosis. We conclude that P-Akt-1 is most likely involved in the progression of prostate cancer and is an excellent biomarker for biochemical recurrence.