Transcriptomic and Clinical Characterization of Neuropeptide Y Expression in Localized and Metastatic Prostate Cancer: Identification of Novel Prostate Cancer Subtype with Clinical Implications (European Urology Oncology)

Herein, we characterize the clinical role of neuropeptide Y (NPY) that is prostate specific in >18000 primary prostate adenocarcinomas, and >300 metastatic castrate-resistant prostate cancer (mCRPC) and treatment-induced neuroendocrine carcinomas.We first show that low NPY is associated with higher Gleason grade tumors, higher genomic risk scores, and poorer metastasis-free survival in primary tumors. In mCRPC, low NPY was associated with neuroendocrine development.ERG was highly correlated to NPY. Thus, we defined four subgroups based on NPY expression and ERG fusion (lowNPY/ERG+, lowNPY/ERG-, highNPY/ERG+, and highNPY/ERG-). The lowNPY/ERG+ subtype was associated with the highest genomic risk for metastasis and the highest rate of metastasis compared with all other subtypes across multiple cohorts. Differential gene expression showed that genes downregulated in lowNPY/ERG+ are enriched with androgen receptor targets. Prognostic subgrouping and tailored treatments by NPY expression and ERG fusion status warrant further study.