Transcriptomic Heterogeneity of Gleason Grade Group 5 Prostate Cancer

Gleason grade group (GG) 5 prostate cancer has been associated with an aggressive natural history, and retrospective data support a role for treatment intensification. However, clinical outcomes remain heterogeneous in this cohort, and intensified treatments carry an increased risk of adverse events...

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Bibliographic Details
Published in:European urology 2020-09, Vol.78 (3), p.327-332
Main Authors: Kishan, Amar U., Romero, Tahmineh, Alshalalfa, Mohammed, Liu, Yang, Tran, Phuoc T., Nickols, Nicholas G., Ye, Huihui, Sajed, Dipti, Rettig, Matthew B., Reiter, Robert E., Garraway, Isla P., Spratt, Daniel E., Freedland, Steven J., Zhao, Xin, Li, Ziwen, Deek, Matthew, Livingstone, Julie, Mahal, Brandon A., Nguyen, Paul L., Feng, Felix Y., Den, Robert B., Schaeffer, Edward M., Lotan, Tamara L., Karnes, R. Jeffrey, Klein, Eric A., Ross, Ashley E., Grogan, Tristan, Davicioni, Elai, Elashoff, David, Boutros, Paul C., Weidhaas, Joanne B.
Format: Article
Language:English
Subjects:
Aged
Biomarkers
Cohort Studies
Genetic Variation
Gleason grade group 5
Gleason score 10
Gleason score 9
Humans
Male
Middle Aged
Neoplasm Grading
Prostatic Neoplasms - genetics
Prostatic Neoplasms - pathology
Transcriptome
Transcriptomics
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Summary:Gleason grade group (GG) 5 prostate cancer has been associated with an aggressive natural history, and retrospective data support a role for treatment intensification. However, clinical outcomes remain heterogeneous in this cohort, and intensified treatments carry an increased risk of adverse events. We sought to explore the transcriptomic heterogeneity of GG 5 tumors by querying transcriptomic data from the tumors of 2138 patients with GG 5 disease who underwent prostatectomy. Four distinct consensus clusters were identified with respect to differential transcriptional activation of hallmark pathways, with distinct molecular subtyping profiles and different average genomic risks (AGRs). One cluster, accounting for 325 tumors (15.2% of the population), was enriched for genes related to the cell cycle/proliferation, metabolic pathways, androgen response pathways, and DNA repair, and had a higher AGR than the other clusters (p 
ISSN:0302-2838
1873-7560
DOI:10.1016/j.eururo.2020.05.009