Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer.

摘要: Intratumoral androgen biosynthesis is one of the mechanisms involved in progression prostate cancer, and an important target for novel cancer therapies. Using gas chromatography-tandem mass spectrometry genome-wide RNA sequencing, we have analyzed concentrations androgen-regulated gene expression cancerous morphologically benign tissue specimens serum samples obtained from 48 primary patients. dihydrotestosterone (DHT) were significantly higher tissues compared to (P < 0.001). The tissue/serum ratios androgens highly variable between patients, indicating individual patterns metabolism and/or uptake within tissue. An unsupervised hierarchical clustering analysis intratissue indicated that transmembrane protease, serine 2/ETS-related (TMPRSS2-ERG)-positive patients different profiles TMPRSS2-ERG-negative TMPRSS2-ERG fusion status was also associated with enhanced expression, along altered intratumoral metabolism, demonstrated by reduced testosterone increased DHT/testosterone TMPRSS2-ERG-positive tumors. -negative distinct profiles, possibly due activation testosterone-independent DHT via alternative pathway Thus, may benefit inhibitors targeting biosynthesis.