Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNAseq Analysis of Formalin-Fixed Paraffin-Embedded Prostate Cancer Tissues

ABSTRACT: In an effort to identify biomarkers of recurrence, we have performed global RNA-sequencing on 106 formalin-fixed, paraffin-embedded (FFPE) prostatectomy samples from 100 patients at three independent sites, and identified a new set of biomarkers of biochemical recurrence composed of a 24-gene panel. We validated this 24-gene panel on an independent publicly available dataset of 140 patients and this new panel outperformed previously published markers based on cell proliferation gene sets in terms of prediction of biochemical recurrence (BCR). In addition we identified differences in gene expression between Gleason Pattern 4+3 and Gleason Pattern 3+4 tumors. 106 samples from 100 patients were sequenced. Six samples were sequenced from two independent RNA preps and libraries. All samples were taken from FFPE Radical Prostatectomies. Samples were obtained from Atlanta VA Medical Center, U. Toronto Sunnybrook Research Centre, and Moffitt Cancer Center.

ORGANISM(S): Homo sapiens

SUBMITTER: Carlos Moreno

PROVIDER: E-GEOD-54460 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Global transcriptome analysis of formalin-fixed prostate cancer specimens identifies biomarkers of disease recurrence.

Long Qi Q Xu Jianpeng J Osunkoya Adeboye O AO Sannigrahi Soma S Johnson Brent A BA Zhou Wei W Gillespie Theresa T Park Jong Y JY Nam Robert K RK Sugar Linda L Stanimirovic Aleksandra A Seth Arun K AK Petros John A JA Moreno Carlos S CS

Cancer research 20140408 12

Prostate cancer remains the second leading cause of cancer death in American men and there is an unmet need for biomarkers to identify patients with aggressive disease. In an effort to identify biomarkers of recurrence, we performed global RNA sequencing on 106 formalin-fixed, paraffin-embedded prostatectomy samples from 100 patients at three independent sites, defining a 24-gene signature panel. The 24 genes in this panel function in cell-cycle progression, angiogenesis, hypoxia, apoptosis, PI3 ...[more]

PMID: 24713434

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Project description:Purpose: Clinicopathologic features and biochemical recurrence are sensitive, but not specific, predictors of metastatic disease and lethal prostate cancer. We hypothesize that a genomic expression signature detected in the primary tumor represents true biological potential of aggressive disease and provides improved prediction of early prostate cancer metastasis. Methods: A nested case-control design was used to select 639 patients from the Mayo Clinic tumor registry that underwent radical prostatectomy between 1987 and 2001. A genomic classifier (GC) was developed by modeling differential RNA expression using 1.4 million feature high-density expression arrays of men enriched for rising PSA after prostatectomy, including 213 that experienced early clinical metastasis after biochemical recurrence. A training set was used to develop a random forest classifier of 22 markers to predict for cases - men with early clinical metastasis after rising PSA. Performance of GC was compared to prognostic factors such as Gleason score and previous gene expression signatures in a withheld validation set. Results: Expression profiles were generated from 545 unique patient samples, with median follow-up of 16.9 years. GC achieved an area under the receiver operating characteristic curve of 0.75 (0.67 - 0.83) in validation, outperforming clinical variables and gene signatures. GC was the only significant prognostic factor in multivariable analyses. Within Gleason score groups, cases with high GC scores experienced earlier death from prostate cancer and reduced overall survival. The markers in the classifier were found to be associated with a number of key biological processes in prostate cancer metastatic disease progression. Conclusion: A genomic classifier was developed and validated in a large patient cohort enriched with prostate cancer metastasis patients and a rising PSA that went on to experience metastatic disease. This early metastasis prediction model based on genomic expression in the primary tumor may be useful for identification of aggressive prostate cancer. 545 formalin-fixed paraffin-embedded (FFPE) tissue samples from primary prostate cancer obtained from Radical Prostatectomy.

Dataset Information

RNAseq Analysis of Formalin-Fixed Paraffin-Embedded Prostate Cancer Tissues

Publications

Global transcriptome analysis of formalin-fixed prostate cancer specimens identifies biomarkers of disease recurrence.

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