Changes of Transthyretin and Clusterin after Androgen Ablation Therapy and Correlation with Prostate Cancer Malignancy12

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