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雄激素剥夺治疗后转甲状腺素和簇集素的变化及其与前列腺癌恶性程度的关系。

Changes of transthyretin and clusterin after androgen ablation therapy and correlation with prostate cancer malignancy.

机构信息

Department of Urology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

出版信息

Transl Oncol. 2012 Apr;5(2):124-32. doi: 10.1593/tlo.11259. Epub 2012 Apr 1.

Abstract

After androgen ablation therapy (AAT), advanced prostate cancer (Pca) eventually progresses to castration-resistant Pca (CRPC); however, the biomarkers that are used to predict its prognosis are limited. In this study, serum samples from four patients with advanced Pca were collected at the time of the initial diagnosis and 3 months after AAT. Proteomic changes were analyzed with two-dimensional differential in-gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Altogether, nine proteins were differentially expressed in the samples collected at diagnosis and in the samples collected after AAT. Among them, the expression of transthyretin (TTR) was 1.58-fold lower and clusterin (CLU) was 1.51-fold higher in the sera of post-AAT patients compared with those in the sera from pre-AAT patients. The significant changes in serum TTR and CLU in post-AAT patients were further confirmed by a large-scale ELISA. Immunohistochemistical staining revealed that the expression levels of TTR and CLU were significantly higher in Pca tissue than in normal and benign prostate hyperplasia tissue. The expression levels of TTR and CLU in Pca tissue were found to be associated with the grade and stage of Pca. Overall, this study indicated that TTR and CLU might be used to monitor the efficacy of AAT therapy and serve as biomarkers for the prognosis of Pca.

摘要

雄激素剥夺治疗 (AAT) 后,晚期前列腺癌 (Pca) 最终进展为去势抵抗性 Pca (CRPC);然而,用于预测其预后的生物标志物是有限的。在这项研究中,在初始诊断时和 AAT 后 3 个月采集了 4 例晚期 Pca 患者的血清样本。使用二维差异凝胶电泳和基质辅助激光解吸/电离飞行时间质谱分析蛋白质组学变化。总共,在诊断时采集的样本和 AAT 后采集的样本中,有 9 种蛋白质表达差异。其中,与 AAT 前患者的血清相比,AAT 后患者的血清中转甲状腺素 (TTR) 的表达降低了 1.58 倍,而簇蛋白 (CLU) 的表达升高了 1.51 倍。通过大规模 ELISA 进一步证实了 AAT 后患者血清中 TTR 和 CLU 的显著变化。免疫组织化学染色显示,TTR 和 CLU 在 Pca 组织中的表达水平明显高于正常和良性前列腺增生组织。发现 TTR 和 CLU 在 Pca 组织中的表达水平与 Pca 的分级和分期有关。总体而言,这项研究表明 TTR 和 CLU 可能用于监测 AAT 治疗的疗效,并作为 Pca 预后的生物标志物。

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