Prostate epithelial genes define therapy-relevant prostate cancer molecular subtype.

BACKGROUND AND OBJECTIVES: Transcriptomic landscape of prostate cancer (PCa) shows multidimensional variability, potentially arising from the cell-of-origin, reflected in serum markers, and most importantly related to drug sensitivities. For example, Aggressive Variant Prostate Cancer (AVPC) presents low PSA per tumor burden, and characterized by de novo resistance to androgen receptor signaling inhibitors (ARIs). Understanding PCa transcriptomic complexity can provide biological insight and therapeutic guidance. However, unsupervised clustering analysis is hindered by potential confounding factors such as stromal contamination and stress-related material degradation. MATERIALS AND METHODS: To focus on prostate epithelial cell-relevant heterogeneity, we defined 1,629 genes expressed by prostate epithelial cells by analyzing publicly available bulk and single- cell RNA sequencing data. Consensus clustering and CIBERSORT deconvolution were used for class discovery and proportion estimate analysis. The Cancer Genome Atlas Prostate Adenocarcinoma dataset served as a training set. The resulting clusters were analyzed in association with clinical, pathologic, and genomic characteristics and impact on survival. Serum markers PSA and PAP was analyzed to predict response to docetaxel chemotherapy in metastatic setting. RESULTS: We identified two luminal subtypes and two aggressive variant subtypes of PCa: luminal A (Adipogenic/AR-active/PSA-high) (30.0%); luminal S (Secretory/PAP-high) (26.0%); AVPC-I (Immune-infiltrative) (14.7%), AVPC-M (Myc-active) (4.2%), and mixed (25.0%). AVPC-I and AVPC-M subtypes predicted to be resistant to ARI and have low PSA per tumor burden. Luminal A and AVPC-M predicted to be resistant to docetaxel and have high PSA/PAP Ratio. Metastatic PCa patients with high PSA/PAP ratio (>20) had significantly shorter progression-free survival than those with low ratio (≤20) following docetaxel chemotherapy. CONCLUSION: We propose four prostate adenocarcinoma subtypes with distinct transcriptomic, genomic, and pathologic characteristics. PSA/PAP ratio in advanced cancer may aid in determining which patients would benefit from maximized androgen receptor inhibition or early use of antimicrotubule agents.

Phosphorus as predictive factor for erectile dysfunction in middle aged men: A cross sectional study in Korea.

PURPOSE: High serum inorganic phosphorus level is related with atherosclerosis and an elevated risk of cardiovascular disease. At the same time, the association of phosphorus with erectile dysfunction (ED) is not well reported. We studied the effect of serum phosphorus on ED and the relationship with other clinical variables. MATERIALS AND METHODS: From March to September 2013, 1,899 police men aged 40 to 59 years who entered in a prostate health screening were targeted. All subjects underwent a clinical checking using the International Index of Erectile Function-5 (IIEF-5) questionnaire translated into Korean. Serum prostate-specific antigen (PSA), testosterone, inorganic phosphorus, body mass index, metabolic syndrome (MetS), and prostate ultrasound were also examined. RESULTS: Serum inorganic phosphorus (r=-0.108, p<0.001) had the highest correlation coefficient with IIEF-5 score other than age, followed by prostate volume (PV) (r=-0.065, P<0.001). Using logistic regression analysis, age, phosphorus, and MetS were predictive factors for moderate to severe ED in univariate analysis. PSA, testosterone, body mass index, and PV could not predict ED. Age, MetS, and phosphorus were independent predictive factors of moderate to severe ED (p<0.001; odds ratio [OR], 1.119; 95% confidence interval [CI] 1.086-1.153; p=0.048; OR, 1.283; 95% CI, 1.003-1.641; and p=0.048; OR, 1.101; 95% CI, 1.076-1.131) in the multivariate analysis. CONCLUSIONS: In our study, phosphorus level is related with ED. Phosphorus is a significant predictor of ED and a strong factor that can be modified in the middle-age. Controlling phosphorus in men may have a particular meaning of preventing the occurrence of ED.