Luminal and basal subtyping of prostate cancer
| Autor: | Robert B. Den, Matthew R. Cooperberg, Nicholas Erho, Charles J. Ryan, Peter R. Carroll, Elai Davicioni, Jeffrey Karnes, Eric A. Klein, Stephen J. Freedland, Mohammed Alshalalfa, Edward M. Schaeffer, Seiwon Laura Chang, Edwin M. Posadas, Felix Y. Feng, Shuang G. Zhao, Daniel E. Spratt, Paul L. Nguyen, Jonathan Lehrer, Ashley E. Ross, Won Kim |
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| Rok vydání: | 2017 |
| Předmět: |
Oncology
PCA3 medicine.medical_specialty Cancer Research business.industry 030232 urology & nephrology Luminal a medicine.disease Subtyping 03 medical and health sciences Prostate cancer Basal (phylogenetics) 0302 clinical medicine Breast cancer medicine.anatomical_structure Prostate 030220 oncology & carcinogenesis Internal medicine medicine Microarray platform business |
| Zdroj: | Journal of Clinical Oncology. 2017:3-3 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | 3 Background: There is a clear need to develop a clinically relevant molecular subtyping approach for prostate cancer. We hypothesized that prostate cancer can be subtyped based on luminal versus basal lineage. Methods: We applied the PAM50 classifier, which is used clinically to identify luminal and basal cancers in breast cancer, to subtype a total of 3,782 prostate cancer samples using a high-density microarray platform run in a CLIA-certified laboratory. We examined the associations of these subtypes and clinical outcomes. Results: We demonstrate that PAM50 segregates prostate cancer into three reproducible subtypes in both retrospective cohorts and on prospective validation: luminal A (33.3%-34.3%), luminal B (28.5%-32.6%), and basal (34.1%-37.1%). Luminal B prostate cancers exhibited the worst clinical prognoses, followed by basal and luminal A subtypes (10-year biochemical recurrence-free survival: 29/39/41%; distant metastasis-free survival: 53/73/73%; prostate cancer-specific survival: 78/86/89%; overall survival: 69/80/82% respectively) on both univariable and multivariable analyses accounting for standard clinicopathologic prognostic factors. Known luminal lineage markers, such as NKX3.1 and KRT18, and the basal lineage CD49f signature, were enriched in luminal- and basal-like cancers respectively, demonstrating the connection between these subtypes and established prostate cancer biology. While both luminal-like subtypes were associated with increased AR expression and signaling, only luminal B prostate cancers were significantly associated with post-operative response to androgen deprivation therapy (ADT) in a subset analysis matching patients based on clinicopathologic variables (interaction p = 0.006, luminal B 10-year metastasis: 33% (treated) vs. 55% (untreated), non-luminal B: 37% (treated) vs. 21% (untreated)). Conclusions: These findings contribute novel insight into the biology of prostate cancer, and provide translatable clinical tools for personalizing post-operative ADT for patients with prostate cancer. Similar to breast cancer, these findings suggest that luminal/basal subtyping may be useful in treatment selection in prostate cancer. |
| Databáze: | OpenAIRE |
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