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- W2599694538 abstract "38 Background: The Androgen-receptor (AR) signaling plays a pivotal role in prostate cancer initiation and progression. AR amplification and overexpression have been associated with lethal PCa and CRPC; however, much of the impact of these events on cancer progression is poorly understood with an unclear prognostic significance of down-stream targets of AR. Methods: A total of 2,555 RP expression profiles were extracted from the Decipher GRID database; 262 of which were from retrospective natural history cohort with known metastasic outcomes and the remaining from anonymized prospective cases with basic demographic and pathological data available. We built a 9 gene AR-output signature (ARoS) score based on canonical androgen regulated genes to represent AR-output activity in RP tissues. The 9 genes were weighted based on their distribution skewness in the prospective data (n = 2,293) and then scores were calculating by summing the weighted expression of the 9 genes. Results: AR expression and ARoS score were not strongly correlated with approximately 50% of samples with low ARoS have relatively high AR expression. In a prospective cohort of 2,293 patients, low ARoS was associated with higher Decipher metastasis risk scores (OR: 3.1, p < 0.001), higher Gleason grade (OR: 2.4, p < 0.001), ERG-fusion negative (OR: 1.8, p < 0.001) and SVI (OR: 2.1, p < 0.001). Additionally, low ARoS was associated with higher expression of neuroendocrine biomarkers (NCAM1, ENO2). In a large retrospective cohort with long term clinical follow-up, patients with low ARoS score had a higher probability of 10-year metastasis rate (p = 0.002). In 55 patients from this cohort who received ADT post metastasis, the ARoS signature derived from primary tissue was lower in patients who developed CRPC (p < 0.001). Furthermore, ARoS was significantly lower in mCRPC samples (p < 0.001) compared to primary PCa tissues. Conclusions: ARoS derived from primary prostate cancer tissue is correlated with metastatic outcomes and progression to CRPC. With further validation, such a signature may better predict those patients which require early intensification of systemic therapy." @default.
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- W2599694538 date "2017-02-20" @default.
- W2599694538 modified "2023-09-22" @default.
- W2599694538 title "Relationships between an androgen receptor output signature (ARoS), AR expression, and poor prostate cancer prognosis in RP tissues." @default.
- W2599694538 doi "https://doi.org/10.1200/jco.2017.35.6_suppl.38" @default.
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