Molecular heterogeneity in prostate cancer (PCa) is one of the key reasons underlying the differing likelihoods of recurrence after surgical treatment in individual patients of the same clinical category. In this study, we performed RNA-Seq profiling of 58 localized PCa and 43 locally advanced PCa tissue samples obtained as a result of radical prostatectomy on a cohort of Russian patients. Based on bioinformatics analysis, we examined features of the transcriptome profiles within the high-risk group, including within the most commonly represented molecular subtype, TMPRSS2-ERG. The most significantly affected biological processes in the samples were also identified, so that they may be further studied in the search for new potential therapeutic targets for the categories of PCa under consideration. The highest predictive potential was found with theEEF1A1P5,RPLP0P6,ZNF483,CIBAR1,HECTD2,OGN, andCLIC4genes. We also reviewed the main transcriptome changes in the groups at intermediate risk of PCa—Gleason Score 7 (groups 2 and 3 according to the ISUP classification)—on the basis of which theLPL,MYC, andTWIST1genes were identified as promising additional prognostic markers, the statistical significance of which was confirmed using qPCR validation.