Gene expression signature predicts biochemical and metastatic recurrence in men with clinically localized prostate cancer treated with radical prostatectomy.
Prostate cancer (PCa) risk stratification is based on tumour size, PSA level and Gleason Score, but it remains imprecise. Current research focuses on the discovery of novel biomarkers to improve the identification of patients at risk of tumour progression. The purpose of this study was to develop a gene expression signature for predicting tumour progression after radical prostatectomy.
Retrospective study which includes 188 PCa patients who attended at our department between 2000 and 2007. Formalin-fixed paraffin embedded PCa tissue samples were collected. Global gene expression patterns were analysed in 21 selected samples from 7 localized, 6 locally advanced, and 8 metastatic PCa patients using Illumina microarrays. Expression levels of 45 genes selected from microarray data and literature were studied by quantitative PCR in an independent series of 167 patients who underwent radical prostatectomy for clinically localized PCa and with ≥ 10 years follow-up. Biochemical recurrence (BCR) was defined as 2 consecutive PSA values ≥ 0.2ng/mL or salvage treatment 6 months after prostatectomy. Univariate and multivariate logistic regression analysis was used to identify individual predictors of BCR and metastatic recurrence. Kaplan Meier curves were used to discriminate two groups of localized PCa patients with different probability of progression.
Median follow-up of the series was 131.8 months (120-194). During the surveillance period, 55 patients developed BCR (33%) and 6 metastatic recurrence (3.6%). Overall, three patients died of PCa (1.8%), and 22 due to other causes (13%). Expression levels of 15800 genes differed between clinically localized and locally advanced-metastatic PCa groups (FDR<0.1). A total of 35 differently expressed genes with a fold change value > 5 and 10 genes previously described in literature were selected to be validated in an additional set of samples. Two genes were found to be independent prognostic factors of BCR (MSMB, HR=1.75, p=0.04) (FOS, HR=1.73, p=0.05) and two genes were found to be predictors of metastatic recurrence (KRT17, HR=7.17, p=0.03) (SERPINE1, HR=5.54, p=0.06).
Gene expression levels in PCa tissue can be useful for distinguishing patients with clinically localized disease who will develop BCR or metastatic recurrence after radical prostatectomy. These gene expression biomarkers could have potential clinical utility for identifying the subset of patients that would benefit from closer surveillance and adjuvant therapy.