Plasma extracellular vesicle circRNA signature and resistance to abiraterone in metastatic castration-resistant prostate cancer.

BACKGROUND: We aimed to develop and validate a plasma extracellular vesicle circular RNA (circRNA)-based signature that can predict overall survival (OS) in first-line abiraterone therapy for metastatic castration-resistant prostate cancer (mCRPC) patients. METHODS: In total, 582 mCRPC patients undergoing first-line abiraterone therapy from four institutions were sorted by three phases. In the discovery phase, 30 plasma samples from 30 case-matched patients with or without early progression were obtained to generate circRNA expression profiles using RNA sequencing. In the training phase, differentially expressed circRNAs were examined using digital droplet PCR in a training cohort (n = 203). The circRNA signature was constructed using a least absolute shrinkage and selection operator Cox regression to predict OS. In the validation phase, the prognostic ability of this signature was prospectively validated in two external cohorts (Cohort I, n = 183; Cohort II, n = 166). RESULTS: We developed a five-circRNA signature, based on circCEP112, circFAM13A, circBRWD1, circVPS13C and circMACROD2, which successfully stratified patients into high-risk and low-risk groups. The prognostic ability of this signature was prospectively validated in two external cohorts (P < 0.0001, P < 0.0001). Patients with high-risk scores had shorter OS than patients with low-risk scores. CONCLUSION: This five-circRNA signature is a reliable predictor of OS for mCRPC patients undergoing abiraterone.

A urine extracellular vesicle lncRNA classifier for high-grade prostate cancer and increased risk of progression: A multi-center study.

To construct a urine extracellular vesicle long non-coding RNA (lncRNA) classifier that can detect high-grade prostate cancer (PCa) of grade group 2 or greater and estimate the risk of progression during active surveillance, we identify high-grade PCa-specific lncRNAs by combined analyses of cohorts from TAHSY, TCGA, and the GEO database. We develop and validate a 3-lncRNA diagnostic model (Clnc, being made of AC015987.1, CTD-2589M5.4, RP11-363E6.3) that can detect high-grade PCa. Clnc shows higher accuracy than prostate cancer antigen 3 (PCA3), multiparametric magnetic resonance imaging (mpMRI), and two risk calculators (Prostate Cancer Prevention Trial [PCPT]-RC 2.0 and European Randomized Study of Screening for Prostate Cancer [ERSPC]-RC) in the training cohort (n = 350), two independent cohorts (n = 232; n = 251), and TCGA cohort (n = 499). In the prospective active surveillance cohort (n = 182), Clnc at diagnosis remains a powerful independent predictor for overall active surveillance progression. Thus, Clnc is a potential biomarker for high-grade PCa and can also serve as a biomarker for improved selection of candidates for active surveillance.

[Expressions of CD4+ CD25(high) regulatory T cells, TGF-beta 1 and COX-2 in the peripheral blood of prostate cancer patients].

OBJECTIVE: To investigate the expressions of CD4+ CD25(high) regulatory T cells, TGF-beta 1 and COX-2 in the peripheral blood of prostate cancer (PCa) patients, and analyze the role of CD4+ CD25(high) regulatory T cells in the pathogenesis of PCa and their relationship with TGF-beta 1 and COX-2. METHODS: We used flow cytometry to calculate the percentage of CD4+ CD25(high) regulatory T cells in the CD4+ T cells in the peripheral blood mononuclear cells (PBMC) from 30 PCa patients (11 localized and 19 non-localized cases) and 20 healthy volunteer controls, determined the expressions of TGF-beta 1 and COX-2 in the serum by ELISA, and analyzed their correlation with the CD4+ CD25(high) regulatory T cells in the PCa patients as well as the differences between the localized and non- localized cases. RESULTS: CD4+ CD25(high) regulatory T cells accounted for (18.32 +/- 7.49) % in the CD4+ T cells in PBMCs from the PCa patients, significantly higher than (7.77 +/- 1.86) % from the controls (P < 0.05), but with no statistically significant difference between pre- and post-treatment in the PCa patients (P > 0.05). The expressions of TGF-beta 1 and COX-2 in the peripheral blood were (215.97 +/- 55.16) ng/ml and (6.88 +/- 5.14) ng/ml in the PCa patients, in comparison with (149.75 +/- 47.11) ng/ml (P < 0.05) and (6.88 +/- 5.14) ng/ml (P > 0.05) in the controls. Multiple linear regression analysis showed no significant correlation between the expression of CD4+ CD25(high) regulatory T cells in PBMCs and those of TGF-beta 1 and COX-2 in the peripheral blood of the PCa patients. There were no significant differences between the localized and non-localized PCa groups in the expressions of CD4+ CD25(high) regulatory T cells, TGF-beta 1 and COX-2 (P > 0.05). CONCLUSION: CD4+ CD25(high) regulatory T cells in in PBMCs are involved in the pathogenesis of PCa. The proliferation of CD4+ CD25(high) regulatory T cells is not significantly correlated to the expressions of TGF-beta 1 and COX-2 in the peripheral blood, but maybe to the tumor itself and the local tumor microenvironment.

Prediction of potential prognostic biomarkers in metastatic prostate cancer based on a circular RNA-mediated competing endogenous RNA regulatory network.

Recently, studies on competing endogenous RNA (ceRNA) networks have become prevalent, and circular RNAs (circRNAs) have crucial implications for the development and progression of carcinoma. However, studies relevant to metastatic prostate cancer (mPCa) are scant. This study aims to discover potential ceRNAs that may be related to the prognosis of mPCa. RNA-Seq data were obtained from the MiOncoCirc database and Gene Expression Omnibus (GEO). Differential expression patterns of RNAs were examined using R packages. Circular RNA Interactome, miRTarBase, miRDB and TargetScan were applied to predict the corresponding relation between circRNAs, miRNAs and mRNAs. The Gene Ontology (GO) annotations were performed to present related GO terms, and Gene Set Enrichment Analysis (GSEA) tools were applied for pathway annotations. Moreover, survival analysis was conducted for the hub genes. We found 820 circRNAs, 81 miRNAs and 179 mRNAs that were distinguishingly expressed between primary prostate cancer (PCa) and mPCa samples. A ceRNA network including 45 circRNAs, 24 miRNAs and 56 mRNAs was constructed. In addition, the protein-protein interaction (PPI) network was built, and 10 hub genes were selected by using the CytoHubba application. Among the 10 hub genes, survival analysis showed that ITGA1, LMOD1, MYH11, MYLK, SORBS1 and TGFBR3 were significantly connected with disease-free survival (DFS). The circRNA-mediated ceRNA network provides potential prognostic biomarkers for metastatic prostate cancer.

Comparison of penile size and erectile function after high-intensity focused ultrasound and targeted cryoablation for localized prostate cancer: a prospective pilot study.

INTRODUCTION: Erectile dysfunction (ED) represents a common quality-of-life issue of any treatment used for prostate cancer, including high-intensity focused ultrasound (HIFU) and targeted cryoablation of the prostate (TCAP). There is a paucity of comparative studies regarding the difference in the erectile function and penile size of patients undergoing HIFU or TCAP. AIM: The aim of this study is to compare the erectile function and penile size of patients undergoing HIFU or TCAP. METHODS: Patients with a preoperative erectile function domain of the International Index of Erectile Function (IIEF-EF) score ≥ 26 were prospectively included. All patients were preoperatively evaluated by IIEF-EF and penile color Doppler ultrasound. Penile length and circumference were measured in flaccidity and at maximum erection. At 6, 12, 18, 24, 36 months after surgery, patients were assessed with the same protocol. MAIN OUTCOME MEASURES: IIEF-EF score, penile color Doppler ultrasound, penile length, and circumference at different time points. RESULTS: There were 55 patients in the HIFU group and 47 in the TCAP group. At each time point, there were significant differences in mean IIEF-EF scores and penile color Doppler results between the two groups. At 36 months, TCAP patients experienced lower erectile function recovery rate compared with HIFU patients (TCAP=46.8%; HIFU=65.5%; P=0.021). No significant decreases in penile length and circumference were found in the two groups (all P values ≥ 0.05). CONCLUSIONS: Our data demonstrate TCAP caused significantly decreased erectile function than HIFU. We found no change in penile size after HIFU or TCAP. The option of HIFU may be more attractive to the patient who wants to avoid ED afterward, to maintain their quality of life.