Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The Wnt/β-catenin-signaling pathway is modulated by androgen ablation therapy for advanced clinical prostate cancer and contributes to androgen independent cell growth

ABSTRACT: Androgen ablation therapy (AAT) is standard treatment for locally-advanced/metastatic prostate cancer (PCa). Many patients develop castration-resistance (CRPCa) after ~2-3 years, with a poor prognosis. The molecular mechanisms underlying CRPCa progression are unclear. mRNA-Seq was performed on tumours from 7 patients with locally-advanced/metastatic PCa before and ~22 weeks after AAT initiation. Differentially regulated genes were identified in treatment pairs. Tumour biopsies from 7 patients were taken before and after AAT treatment

ORGANISM(S): Homo sapiens

SUBMITTER: Ian Sudbery

PROVIDER: E-GEOD-48403 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy.

Rajan Prabhakar P Sudbery Ian M IM Villasevil M Eugenia M ME Mui Ernest E Fleming Janis J Davis Mark M Ahmad Imran I Edwards Joanne J Sansom Owen J OJ Sims David D Ponting Chris P CP Heger Andreas A McMenemin Rhona M RM Pedley Ian D ID Leung Hing Y HY

European urology 20130814 1

<h4>Background</h4>Androgen-deprivation therapy (ADT) is standard treatment for locally advanced or metastatic prostate cancer (PCa). Many patients develop castration resistance (castration-resistant PCa [CRPC]) after approximately 2-3 yr, with a poor prognosis. The molecular mechanisms underlying CRPC progression are unclear.<h4>Objective</h4>To undertake quantitative tumour transcriptome profiling prior to and following ADT to identify functionally important androgen-regulated pathways or gene ...[more]

PMID: 24054872

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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.

Dataset Information

The Wnt/β-catenin-signaling pathway is modulated by androgen ablation therapy for advanced clinical prostate cancer and contributes to androgen independent cell growth

Publications

Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy.

Similar Datasets

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