RESUMO
MicroRNA (miRNA) deregulation plays a critical role in the heterogeneous development of prostate cancer (PCa) by tuning mRNA levels. Herein, we aimed to characterize the molecular features of PCa by clustering the miRNA-regulated transcriptome with non-negative matrix factorization. Using 478 PCa samples from The Cancer Genome Atlas, four molecular subtypes (S-I, S-II, S-III, and S-IV) were identified and validated in two merged microarray and RNAseq datasets with 656 and 252 samples, respectively. Interestingly, the four subtypes showed distinct clinical and biological features after comprehensive analyses of clinical features, multiomic profiles, immune infiltration, and drug sensitivity. S-I is basal/stem/mesenchymal-like and immune-excluded with marked transforming growth factor ß, epithelial-mesenchymal transition and hypoxia signals, increased sensitivity to olaparib, and intermediate prognosis. S-II is luminal/metabolism-active and responsive to androgen deprivation therapy with frequent TMPRSS2-ERG fusion and a good prognosis. S-III is characterized by moderate proliferative and metabolic activity, sensitivity to taxane-based chemotherapy, and intermediate prognosis. S-IV is highly proliferative with moderate EMT and stemness, frequent deletions of TP53, PTEN and RB, and the poorest prognosis; it is also immune-inflamed and sensitive to anti-PD-L1 therapy. Overall, based on miRNA-regulated gene profiles, this study identified four distinct PCa subtypes that could improve risk stratification at diagnosis and provide therapeutic guidance.
RESUMO
PURPOSE: To investigate the impact of prostate weight on outcomes of nerve sparing laparoscopic radical prosta-tectomy (LRP) and assess its predictive value on postoperative continence and potency recovery. MATERIALS AND METHODS: We conducted a retrospective study on the clinical data of 165 patients with low risk prostate cancer (PCa) who underwent nerve sparing LRP. All the patients included had normal preoperative uri-nary and sexual function. The association of prostate weight with perioperative data was assessed using Spearman correlation coefficient. Univariate and multivariate Cox regression analyses were employed to identify prognostic predictors for continence and potency recovery. RESULTS: Increased prostate weight was significantly associated with older age, higher prostate-specific antigen (PSA), lower biopsy and pathological T stage and Gleason score, longer operative time, and higher estimated blood loss (P < .05). The continence rates at the 3rd, 6th, and 12th month after surgery were 63.6% (105/165), 87.9% (145/165), and 95.8% (158/165); and the potency rates were 44.8% (74/165), 62.4% (103/165) and 77.6% (128/165), respectively. Furthermore, multivariate Cox analysis showed that patient age (HR = 0.52, 95% CI: 0.35- 0.76) and prostate weight (HR = 0.54, 95% CI: 0.34-0.86) were independent predictors for continence recovery, while only patient age (HR = 0.66, 95% CI: 0.45-0.96) could independently predict potency recovery. CONCLUSION: Larger prostate size was correlated with older age, higher PSA, lower tumor stage and grade, longer operative time, and more intraoperative blood loss in low risk PCa patients. Increased prostate weight may inde-pendently predict poor continence recovery after nerve sparing LRP.