Validation of a Genomic Classifier for Predicting Post-Prostatectomy Recurrence in a Community Based Health Care Setting

Glass, Andrew G.; Leo, Michael C.; Haddad, Zaid; Yousefi, Kasra; Plessis, Marguerite du; Chen, Chuhe; Choeurng, Voleak; Abdollah, Firas; Robbins, Bruce A.; Ra, Seong; Richert-Boe, Kathryn; Buerki, Christine; Pearson, Kathy H.; Davicioni, Elai; Weinmann, Sheila

doi:10.1016/j.juro.2015.11.044

Cited by 32 publications

(22 citation statements)

References 22 publications

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“…Expression profiling, specimen selection, RNA extraction and microarray hybridization were done in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory facility (GenomeDx Biosciences, San Diego, CA, USA) as previously described (14). Briefly, total RNA was extracted and purified using the RNeasy FFPE kit (Qiagen, Valencia, CA).…”

Section: Methodsmentioning

confidence: 99%

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup

Labbé

Sweeney

Brown

et al. 2017

Clinical Cancer Research

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Purpose Current clinical parameters do not stratify indolent from aggressive prostate cancer (PCa). Aggressive PCa, defined by the progression from localized disease to metastasis, is responsible for the majority of PCa-associated mortality. Recent gene expression profiling has proven successful in predicting the outcome of PCa patients, however they have yet to provide targeted therapy approaches that could inhibit a patient’s progression to metastatic disease. Experimental Design We have interrogated a total of seven primary PCa cohorts (N = 1,900), two metastatic castration resistant PCa datasets (N = 293) and one prospective cohort (N = 1,385) to assess the impact of TOP2A and EZH2 expression on PCa cellular program and patient outcomes. We also performed immunohistochemical staining for TOP2A and EZH2 in a cohort of primary PCa patients (N = 89) with known outcome. Finally, we explored the therapeutic potential of a combination therapy targeting both TOP2A and EZH2 using novel PCa-derived murine cell lines. Results We demonstrate by genome-wide analysis of independent primary and metastatic PCa datasets that concurrent TOP2A and EZH2 mRNA and protein up-regulation selected for a subgroup of primary and metastatic patients with more aggressive disease and notable overlap of genes involved in mitotic regulation. Importantly, TOP2A and EZH2 in PCa cells act as key driving oncogenes, a fact highlighted by sensitivity to combination-targeted therapy. Conclusions Overall, our data supports further assessment of TOP2A and EZH2 as biomarkers for early identification of patients with increased metastatic potential that may benefit from adjuvant or neo-adjuvant targeted therapy approaches.

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Section: Methodsmentioning

confidence: 99%

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup

Labbé

Sweeney

Brown

et al. 2017

Clinical Cancer Research

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“…Multiple studies have externally validated this biomarker signature to predict clinical recurrence in a community setting,[24] metastatic progression,[22, 25-27] and PCSM after radical prostatectomy. [28, 29] These validation studies have shown good discriminatory ability of the test with the AUC ranging between 0.75 and 0.82.…”

Section: Currently Available Testsmentioning

confidence: 99%

“…Almost all studies compared the discriminatory ability of the GC score to clinical prognostic models such as the Cancer of the Prostate Risk Assessment postsurgical (CAPRA-S),[14] Stephenson nomogram,[15] and Eggener risk model[16] demonstrating improved prognostic discrimination when combined. [24-26, 28, 29]…”

Section: Currently Available Testsmentioning

confidence: 99%

Tissue-based biomarkers in prostate cancer

Clinton

Bagrodia²,

Lotan³

et al. 2017

Expert Review of Precision Medicine and Drug Development

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Introduction Prostate cancer is a heterogeneous disease. Existing risk stratification tools based on standard clinlicopathologic variables (prostate specific antigen [PSA], Gleason score, and tumor stage) provide a modest degree of predictive ability. Advances in high-throughput sequencing has led to the development of several novel tissue-based biomarkers that can improve prognostication in prostate cancer management. Areas Covered The authors review commercially-available, tissue-based biomarker assays that improve upon existing risk-stratification tools in several areas of prostate cancer management, including the appropriateness of active surveillance and aiding in decision making regarding the use of adjuvant therapy. Additionally, some of the obstacles to the widespread adoption of these biomarkers and discuss several investigational sources of new biomarkers are discussed. Expert Commentary Work is ongoing to answer pertinent clinical questions in prostate cancer management including which patients should undergo biopsy, active surveillance, receive adjuvant therapy, and what systemic therapy is best in the first-line. Incorporation into novel biomarkers may allow for the incorporation of a ‘personalized’ approach to management. Further validation will be required and questions of cost must be considered before wide scale adoption of these biomarkers. Tumor heterogeneity may impose a ceiling on the prognostic ability of biomarkers using currently available techniques.

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“…This test has subsequently been validated in several additional cohorts [38,39,40 & 43]. The score is continuous but cut points of less than 0.45, 0.45-0.6, and more than 0.6 have been designated as defining a low-, intermediate-, and high-risk group, respectively.…”

Section: Genomic Classifiermentioning

confidence: 99%

New developments in prostate cancer biomarkers

Martin

2016

Current Opinion in Oncology

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Validation of a Genomic Classifier for Predicting Post-Prostatectomy Recurrence in a Community Based Health Care Setting

Abstract: Decipher improves our ability to predict clinical recurrence in prostate cancer and adds precision to conventional pathological prognostic measures.

Cited by 32 publications

References 22 publications

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup

TOP2A and EZH2 Provide Early Detection of an Aggressive Prostate Cancer Subgroup

Tissue-based biomarkers in prostate cancer

New developments in prostate cancer biomarkers

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