The early effects of rapid androgen deprivation on human prostate cancer

The androgen receptor (AR) is the dominant growth factor in prostate cancer. Understanding how it regulates the human transcriptome is of paramount importance. The early effects of castration on human prostate cancer have not previously been studied. In this study 27 patients were medically castrated with degarelix seven days before radical prostatectomy. Resected tumour was compared with matched controlled untreated prostate cancer tissue by means of mass spectrometry, immunohistochemistry and gene expression array (validated by RT-PCR). All patients had castrate levels of serum androgen with reduced levels of intra-prostatic androgen at prostatectomy. Differential expression of known androgen regulated genes (TMPRSS2, KLK3, CAMKK2, FKBP5) was observed. We identified 749 genes downregulated and 908 genes upregulated following castration. AR regulation of AMACR expression and three other genes (FAM129A, RAB27A and KIAA0101) was confirmed. Up-regulation of oestrogen receptor alpha (ESR1) expression was observed in malignant epithelia. This was associated with differential expression of ESR1 regulated genes and correlated with proliferation (Ki67 expression). In total, 27 patients with D'Amico high-risk prostate cancer were administered 240mg degarelix S.C. (donated by Ferring) 7 days before radical prostatectomy . These patients were matched for risk factors (age, serum PSA, tumor grade and stage) with 20 patients undergoing radical prostatectomy without neoadjuvant degarelix . Study and control patients underwent surgery contemporaneously using standard operative technique, with similar ischemic time before sampling described. This GEO submission dataset comprises gene expression data of tumor and benign tissues from Study patients with acceptable RNA quality (RIN > 8). Control samples (GSM181*) have been previously submitted as part of GSE70768. NOTE: The previously deposited Control samples from GSE70768 have not been reprocessed. They are exactly the same values that have already been submitted. Supplementary file Matrix_normalized_68samples.csv represents the entire dataset.