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Gene expression profile of biochemically recurrent prostate cancer

ABSTRACT: Prostate cancer (PCa) is the second most common solid tumor type in men with high mortality rates. This study specifically aimed at identification of molecular biomarkers of PCa showing clinically aggressive course of the disease. Transcriptome analysis of PCa cases with biochemical progression (BCR) and No-BCR cases was performed with human gene expression microarrays. Expression levels of the selected genes were validated by real-time PCR in two independent cohorts of PCa cases (N = 55 and N = 53) and non-cancerous control tissues (NPT; N = 12). Comparison of gene expression profile of BCR and No-BCR cases revealed significant changes in expression levels of 455 genes, and the vast majority of the genes were down-regulated in the recurrent PCa. Quantitative evaluation of gene expression levels identified down-regulation of MT1E and GPR52 expression and up-regulation of EZH2 as the specific biomarkers of PCa progression, but only MT1E expression retained the independent prognostic value in a multivariate model. Aberrant methylation of the two fragments of MT1E promoter was frequent (71% and 60%) in PCa tissues as compared to NPT (p < 0.001) and was significantly associated with decreased expression in one of the PCa cohorts (p < 0.050). In conclusion, the data of our study suggest epigenetic inactivation of MT1E expression as the specific feature of PCa showing the tendency to progress.

ORGANISM(S): Homo sapiens

PROVIDER: GSE89317 | GEO | 2017/05/01

SECONDARY ACCESSION(S): PRJNA351781

REPOSITORIES: GEO

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Project description:Accurate estimation of recurrence risk is needed for optimal treatment of clinically localized prostate cancer (PCa) patients. We combined classical clinicopathological predictors of biochemical recurrence (BCR) and molecular markers into a new risk score for predicting BCR after radical prostatectomy (RP). A retrospective study which included 122 PCa patients who attended our department between 2000 and 2007 was conducted. Total RNA was isolated from formalin-fixed paraffin embedded PCa tissue. Gene expression patterns were analyzed in 21 selected samples from 7 localized, 6 locally advanced, and 8 metastatic PCa patients using Illumina microarrays. Expression levels of 41 genes were validated by quantitative PCR in an independent retrospective series of 101 patients with ≥ 10 years follow-up who underwent RP for clinically localized PCa. Univariate and multivariate logistic regression analysis were used to identify individual predictors of BCR. A risk score (RS) for predicting BCR including clinicopathological and gene expression data was developed and Kaplan-Meier curves were generated. Interaction networks between the genes of the model were built by GeneMANIA Cytoscape plugin. In a median follow-up of 120 months (range 3-190), 37 patients developed BCR (36.6%). Expression levels of 7,930 transcripts differed between clinically localized and locally advanced-metastatic PCa groups (FDR<0.1). A set of 41 genes were validated by quantitative PCR. Regression analysis showed that expression of ASF1B and MCL1 as well as Gleason score, extracapsular extension, seminal vesicle invasion and positive margins were independent prognostic factors of BCR. A RS generated using these gene expression and clinicopathological variables was able to discriminate between two groups of patients with a significantly different probability of BCR (HR 6.24; CI 3.23-12.4, p<0.01), improving the individual discriminative performance of each of these variables on their own. Direct interactions between the two genes of the model were not found. In conclusion, identification of new gene expression patterns associated with a high probability of BCR in clinically localized PCa patients treated with RP, and their combination with clinicopathological variables in a robust, easy-to-use and reliable classifier may contribute to improve PCa risk stratification and, consequently, to tailor treatment and surveillance strategies in these patients.

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Gene expression profile of biochemically recurrent prostate cancer

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