We investigated the role of vasculogenic mimicry (VM) in the progression of prostate cancer (PCa). Ninety-six patients who had undergone prostatectomy for treatment of PCa and for whom a complete record of clinical and follow-up data were available were reviewed. VM and matrix metalloproteinase-2 (MMP-2) were detected by immunohistochemical staining in frozen tissue sections. Relationship between VM and clinicopathological variables was analyzed statistically. Multivariate analyses were performed to assess the prognostic significance of VM. Results showed that out of the 96 PCa cases studied here, VM was detectable in 24 (25%) and was positively correlated with preoperative prostate-specific antigen (PSA) level, Gleason score, pathological stage, lymph node metastasis, seminal vesicle invasion, distant metastasis and PSA doubling time (PSADT). Univariate analysis showed that VM, PSA level, Gleason score, distant metastasis and PSADT were correlated with overall survival (OS), while VM, Gleason score, distant metastasis, local recurrence and PSADT were correlated with disease-free survival (DFS). Multivariable analysis indicated that the presence of VM, higher Gleason score and distant metastasis were the adverse predictors of OS and DFS. A higher widespread staining for MMP-2 was correlated with the VM-positive subgroup. In conclusion, VM mainly exists in the high risk PCa patients and is an independent marker of poor prognosis.

Background: Chemotherapy and gene therapy are used in clinical practice for the treatment of castration-resistant prostate cancer. However, the poor efficiency of drug delivery and serious systemic side effects remain an obstacle to wider application of these drugs. Herein, we report newly designed PEO-PCL micelles that were self-assembled and modified by spermine ligand, DCL ligand and TAT peptide to carry docetaxel and anti-nucleostemin siRNA. Results: The particle size of the micelles was 42 nm, the zeta potential increased from − 12.8 to 15 mV after grafting with spermine, and the optimal N/P ratio was 25:1. Cellular MTT experiments suggested that introduction of the DCL ligand resulted in high toxicity toward PSMA-positive cells and that the TAT peptide enhanced the effect. The expression of nucleostemin was significantly suppressed in vitro and in vivo, and the tumour-inhibition experiment showed that the dual-drug delivery system suppressed CRPC tumour proliferation. Conclusions: This targeted drug delivery system inhibited the G1/S and G2/M mitotic cycle via synergistic interaction of chemotherapeutics and gene drugs.

Emerging evidence has suggested that patients with metastatic prostate cancer will become resistant after receiving docetaxel (DTX) chemotherapy, but the specific regulatory mechanism is still unclear. lincROR is an important oncogenic long noncoding RNA which plays an important role in regulating tumor carcinogenesis and metastasis; however, the underlying mechanism of lincROR functioning in the DTX resistance process of prostate cancer remains largely unknown. In the current study, we found that lincROR is highly expressed in DTX-resistant prostate cancer cell lines and was associated with poor DTX response in patients with metastatic prostate cancer. By using loss- and gain-of-function experiments revealed that lincROR promotes prostate cancer cells growth and DTX resistance in vitro and in vivo. Mechanistic studies demonstrated that lincROR specifically interacts with and stabilizes MYH9 protein, which enhances β-catenin/hypoxia-inducible factor 1-alpha (HIF1α) pathways. Besides, HIF1α could bind with the promoter region of lincROR to activate its transcription, thus forming the lincROR/MYH9/HIF1α positive feedback loop. Moreover, lincROR could be packaged into exosomes in an heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1)-dependent manner and then disseminated chemoresistance phenotype to receipt cells. Overall, our study provides evidence supporting exosome-mediated lincROR activates the β-catenin/HIF1α positive feedback loop by targeting MYH9 protein, which may be exploited for anticancer therapy. Implications: Our findings suggest that targeting hypoxia stress and chemoresistance for therapeutic purposes and lincROR could promote the improvement of treatment responses in patients with DTX-resistant prostate cancer.

OBJECTIVE: The N-myc downstream-regulated gene 1 (NDRG1) has been discovered as a significant gene in the progression of cancers. However, the regulatory mechanism of NDRG1 remained obscure in prostate cancer (PCa). METHODS: The miR-96-5p and NDRG1 expression levels were evaluated in PCa cell lines, prostate tissues, and validated public databases by real-time PCR, western blot analysis, and immunohistochemistry. The function of miR-96-5p and NDRG1 were investigated by wound healing and transwell assays in vitro, and mouse xenograft assay in vivo. The candidate pathway regulated by NDRG1 was conducted by the next-generation gene sequencing technique. Immunofluorescence and luciferase assay was used to detect the relation between miR-96-5p, NDRG1, and NF-κB pathway. RESULTS: Overexpressing NDRG1 suppresses the migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro, and inhibits metastasis in vivo. Moreover, miR-96-5p contributes to NDRG1 deficiency and promotes PCa cell migration and invasion. Furthermore, NDRG1 loss activates the NF-κB pathway, which stimulates p65 and IKBa phosphorylation and induces EMT in PCa. CONCLUSIONS: MiR-96-5p promotes the migration and invasion of PCa by targeting NDRG1 and regulating the NF-κB pathway.

Objective: To estimate the prognostic value of positive surgical margins (PSM) location and perineural invasion (PNI) for biochemical recurrence (BCR) in patients undergoing radical prostatectomy (RP).Methods: All men with prostate cancer (PCa) who received RP in the second hospital of Tianjin Medical University from 2014 to 2018 were retrospectively identified. All patients met the following criteria: no neoadjuvant or adjuvant treatment, absence of lymph node invasion, or distant metastasis confirmed by surgery or imaging. Comparisons were made between cases with only apex positive (AM), isolated nonapical positive (OM), multiple positive (MM), and negative surgical margins (NSM). Patients were also subdivided according to the Gleason score and pathological tumor stage for analysis.Results: A total of 416 patients available for analysis, of which 132 (31.7%) were PSM, 43 were AM, 37 were OM, and 52 were MM at a median follow-up of 27 months. The PNI was in 30.5% of patients. BCR occurred in 22.6% of patients during follow-up. Both AM and MM were noticed to be independent predictors of BCR with a hazard ratio of 4.192 (95% CI 2.185–8.042;p< 0.001) and 2.758 (95% CI 1.559–4.880;p< 0.001), respectively, when compared to NSM. Though the correlation was significant in univariate analysis, PNI was not an independent risk factor for BCR (p= 0.369). Subgroup analyses suggested that MM was not particularly predictive for BCR in the Gleason score < 8. The hole Cox regression model for the C-index was 0.843Conclusions: PSM location was a significant independent predictor of BCR in PCa, especially in patients with AM or MM, while PNI is a non-independent risk factor. Compared with other locations, AM has a higher BCR risk.