Vasculogenic mimicry plays an important role in adrenocortical carcinoma.

OBJECTIVES: To determine the prognostic role of vasculogenic mimicry in adrenocortical carcinoma, and to explore its relationship with vascular endothelial growth factor receptor 2 expression. METHODS: A total of 46 samples of adrenocortical carcinoma were collected and reviewed. Vasculogenic mimicry and vascular endothelial growth factor receptor 2 were detected by immunohistochemistry and double staining. Survival analysis was carried out to access pronostic significance. Three-dimensional culture method was applied to test the ability of vasculogenic mimicry formation by adrenocortical carcinoma cell lines SW-13 and H295R. Quantitative polymerase chain reaction and western blotting were used to monitor the expression of vascular endothelial growth factor receptor 2 in SW-13 and H295R. After being treated with specific inhibitor or small interfering ribonucleic acid to downregulate expression of vascular endothelial growth factor receptor 2, vasculogenic mimicry formation and cell prolifration of SW-13 cells were evaluated by 3-D culture and Cell Counting Kit-8 methods. RESULTS: Vasculogenic mimicry was observed in 19 of the 46 (41.30%) adrenocortical carcinoma samples. Both vasculogenic mimicry and vascular endothelial growth factor receptor 2 expressions showed a positive association with Weiss score and TNM stage, whereas vascular endothelial growth factor receptor 2 was also associated with tumor size (all P < 0.05). Vasculogenic mimicry was closely correlated with vascular endothelial growth factor receptor 2 expressions (r = 0.470, P < 0.01). The median overall survival of patients with vasculogenicmimicry-positive or vascular endothelial growth factor receptor 2-positive was shorter than that of patients with vasculogenic mimicry-negative or vascular endothelial growth factor receptor 2-negative (P = 0.001 and 0.028, respectively). The vasculogenic mimicry-forming SW-13 cells expressed higher levels of vascular endothelial growth factor receptor 2 than that of H295R, which was unable to form vasculogenic mimicry on Matrigel. However, downregulation of vascular endothelial growth factor receptor 2 only decreased cell proliferation, but not vasculogenic mimicry formation by SW-13 cells. CONCLUSIONS: Vasculogenic mimicry and overexpression of vascular endothelial growth factor receptor 2 seem to correlate with poor prognostic outcomes in adrenocortical carcinoma. Anti-angiogenesis treatments targeting vascular endothelial growth factor receptor 2 should be combined with therapies targeting vasculogenic mimicry in adrenocortical carcinoma.

Therapeutic implications for localized prostate cancer by multiomics analyses of the ageing microenvironment landscape.

Background: Numerous studies have substantiated the association between aging and the progression of malignant tumors in humans, notably prostate cancer (PCa). Nevertheless, to the best of our knowledge, no studies have comprehensively elucidated the intricate characteristics of the aging microenvironment (AME) in PCa. Methods: AME regulatory patterns were determined using the NMF algorithm. Then an ageing microenvironment index (AMI) was constructed, with excellent prognostic and immunotherapy prediction ability, and its' clinical relevance was surveyed through spatial transcriptomics. Further, the drug response was analysed using the Genomics of Drug Sensitivity in Cancer (GDSC), the Connectivity Map (CMap) and CellMiner database for patients with PCa. Finally, the AME was studied using in vitro and vivo experiments. Results: Three different AME regulatory patterns were identified across 813 PCa patients, associated with distinct clinical prognosis and physiological pathways. Based on the AMI, patients with PCa were divided into the high-score and low-score subsets. Higher AMI score was significantly infiltrated with more immune cells, higher rate of biochemical recurrence (BCR) and worse response to immunotherapy, antiandrogen therapy and chemotherapy in PCa. In addition, we found that the combination of bicalutamide and embelin was capable of suppressing tumor growth of PCa. Besides, as the main components of AMI, COL1A1 and BGLAP act as oncogenes and were verified via in vivo and in vitro experiments. Conclusions: AME regulation is significantly associated with the diversity and complexity of TME. Quantitative evaluation of the AME regulatory patterns may provide promising novel molecular markers for individualised therapy in PCa.

Percutaneous ultrasound-guided radiofrequency ablation treatment and genetic testing for renal cell carcinoma with Von Hippel-Lindau disease.

Percutaneous ultrasound-guided radiofrequency ablation is increasingly being studied in the treatment of renal tumors. Because percutaneous ultrasound-guided radiofrequency ablation is a minimally invasive and nephron-sparing procedure, it is ideally suited for patients with a single kidney, multiple tumors, or contraindications to conventional surgery. We report on a patient with Von Hippel-Lindau (VHL) disease who had multicentric tumors in the single kidney that was successfully treated with percutaneous ultrasound-guided radiofrequncy ablation. The one-year follow-up showed that there was no local recurrence or metastasis. And genetic testing showed the patient had a T to G heterozygotic missense mutation at nucleotide 515 of VHL gene exon 1.

The Development of a Gleason Score-Related Gene Signature for Predicting the Prognosis of Prostate Cancer.

The recurrence of prostate cancer (PCa) is intrinsically linked to increased mortality. The goal of this study was to develop an efficient and reliable prognosis prediction signature for PCa patients. The training cohort was acquired from The Cancer Genome Atlas (TCGA) dataset, while the validation cohort was obtained from the Gene Expression Omnibus (GEO) dataset (GSE70769). To explore the Gleason score (GS)-based prediction signature, we screened the differentially expressed genes (DEGs) between low- and high-GS groups, and then univariate Cox regression survival analysis and multiple Cox analyses were performed sequentially using the training cohort. The testing cohort was used to evaluate and validate the prognostic model's effectiveness, accuracy, and clinical practicability. In addition, the correlation analyses between the risk score and clinical features, as well as immune infiltration, were performed. We constructed and optimized a valid and credible model for predicting the prognosis of PCa recurrence using four GS-associated genes (SFRP4, FEV, COL1A1, SULF1). Furthermore, ROC and Kaplan-Meier analysis revealed a higher predictive efficiency for biochemical recurrence (BCR). The results showed that the risk model was an independent prognostic factor. Moreover, the risk score was associated with clinical features and immune infiltration. Finally, the risk model was validated in a testing cohort. Our data support that the GS-based four-gene signature acts as a novel signature for predicting BCR in PCa patients.

[Transrectal ultrasonography in the etiological diagnosis of male obstructive azoospermia: analysis of 695 cases].

OBJECTIVE: To assess the role of transrectal ultrasonography (TRUS) in the etiological diagnosis of male obstructive azoospermia. METHODS: We retrospectively analyzed the clinical data and TRUS findings of 695 patients with obstructive azoospermia from January 2007 to May 2009. RESULTS: Concerning the etiology of obstructive azoospermia, the main TRUS findings included ejaculatory duct abnormality (29.2%), seminal vesicle abnormality (25.4%) and prostate midline cyst (18.5%). TRUS revealed 203 cases of ejaculatory duct dilation, 177 cases of seminal vesicle abnormality (including 108 with absence or agenesis and 51 with dilation of the seminal vesicle), and 128 cases of prostate midline cyst (including 75 with ejaculatory duct cyst and 39 with Müllerian cyst). Calcification of the verumontanum or ejaculatory duct was suspected to be the causes of obstructive azoospermia in 34 cases. However, no significant etiological abnormality was found in 153 cases. Obvious etiology was shown by TRUS in 78.0% of the patients. CONCLUSION: TRUS can clearly display the structural abnormality of the ejaculatory duct and seminal vesicle, and provide important information on the etiology of male obstructive azoospermia.

Chronic administration of sildenafil modified the impaired VEGF system and improved the erectile function in rats with diabetic erectile dysfunction.

INTRODUCTION: Men frequently develop diabetic erectile dysfunction (DMED), as a result of endothelial dysfunction. DMED patients often have reduced efficacy with phosphodiesterase type 5 inhibitors therapy. AIM: To determine whether chronic sildenafil administration can modify the impaired vascular endothelial growth factor (VEGF) system and improve the erectile function in rats with diabetic erectile dysfunction. METHODS: A group of Sprague Dawley rats (n = 30) with DMED were induced by intraperitoneal injection of streptozotocin (40 mg/kg) and screened by subcutaneous injection of Apomorphine (100 mg/kg). They were then exposed to either vehicle or sildenafil (prescribed in our hospital, 5 mg/kg and 10 mg/kg, respectively) for 10 weeks. An additional nondiabetic and age-matched control group (n = 10) was also allocated and given the routine diet for the same period. Assessments were performed to both groups at 36 hours after the last dose of sildenafil. Penile intracavernous pressure (ICP), mean arterial pressure (MAP), penile tissue morphology, immunohistologic analysis, and Western blot analysis of VEGF, VEGFR1, and eNOS were determined. MAIN OUTCOME MEASURE: Functional, morphological, and proteomical changes on penile structures by the chronic Sildenafil (5 mg/kg and 10 mg/kg, respectively) administration were determined. RESULTS: A significant increase of ICP, ICP/MAP ratio, and area under the curve were observed in the both groups treated by sildenafil (5 mg/kg and 10 mg/kg, respectively), compared with the DMED rats without receiving Sildenafil. Immunohistochemical staining of their penile tissue showed a decrease in VEGF, VEGFR1, and eNOS staining in the controlled group compared with an improvement in the chronic sildenafil administration group. Western blot analysis demonstrated exactly the same results. CONCLUSION: We demonstrated that daily sildenafil administration can restore the impaired VEGF system in the penis of DMED rats and progressively improve both erectile function and endothelial function, suggesting a potential general mechanism of improved signaling through the VEGF/eNOS signaling cascade.

Ureteral triplication combined with right renal ectopia and ureteral cyst.

Ureteral triplication is one of the rarest malformations of the upper urinary tract. We report the case of a 12-year-old girl with right ureteral triplication combined with renal ectopia and ureteral cyst with stenosis at the junction of the ureteral cyst and distal ureter. The ureteral cyst was tailored and tubularized, and the tight junction was removed, as in Hynes-Anderson ureteropyeloplasty; on reevaluation almost 4 years later, kidney function was normal and computed tomography showed a normal kidney and ureter.

A new modified renal vein anastomosis in unilateral dual renal transplantation.

Transplantation of renal allografts inadequate to meet the recipient's metabolic needs has been proposed as a cause of chronic allograft failure. Dual renal transplant is a novel idea to transplant enough nephron mass to solve this problem. According to the current literature, graft renal veins are anastomosed to the external iliac vein or inferior vena cava as venous drainage in the setting of dual renal transplantation. In the presented case, renal blood was returned through one of the grafts back to the systematic circulation through the other renal vein graft. This provides a feasible option for unilateral dual renal transplantation to accomplish renal vein anastomosis in some difficult situations.

[Value of 3D 1H-MRS with body coil at 3T in the differential diagnosis of the prostate cancer].

OBJECTIVE: To assess the value of three dimensional proton magnetic resonance spectroscopy (3D 1H-MRS) with body coil at 3T in the differential diagnosis of prostate cancer. METHODS: Forty patients suspected of prostate cancer underwent MRI and MRS examinations, and then transrectal ultrasound guided prostate biopsy for pathological diagnosis. The MRI and MRS features of benign prostate hyperplasia, prostate cancer and prostatic intraepithelial neoplasia (PIN) were analyzed in comparison with the pathological reports, and the receiver operating characteristic curve was drawn for the diagnosis of cancer from peripheral zones. RESULTS: The examinations were accomplished for all the patients. The mean ratios of (Cho + Cre)/Cit in the interstitial and glandular hyperplasia tissues, the cancer tissue of the central and peripheral glands, the healthy peripheral gland and PIN were 0.75 +/- 0.23, 0.59 +/- 0.14, 1.79 +/- 0.90, 1.18 +/- 0.95, 0.46 +/- 0.18, and 0.97 +/- 0.10, respectively, with statistically significant differences between the cancer and normal prostate tissues (P < 0.01). The optimum threshold for the diagnosis of prostate cancer in the peripheral zone was 0.68 with a sensitivity of 88.6% and a specificity of 88.7%. CONCLUSION: The 3D 1H-MRS with body coil at 3T has a high sensitivity and specificity in the differential diagnosis of prostate cancer, and can provide valuable information for the diagnosis of PIN.

Suppressive dendritic cells as a tool for controlling allograft rejection in organ transplantation: promises and difficulties.

The most important antigen-presenting cells are dendritic cells (DCs), which play a central role in the initiation of immunity and tolerance. Their immunoregulatory properties offer the potential of donor-specific control of graft rejection after organ transplantation. It has not been clarified which DC subpopulations mediate tolerance, and the use of natural DCs for therapeutic applications is therefore problematic. Suppressive DCs can be generated in vitro by treating the cells with biologic, pharmacologic, or genetic agents. Here we discuss approaches for generating inhibitory DCs and present DC-based animal models for control of allograft rejection. A prerequisite of suppressive DCs for therapeutic application in clinical transplantation is a reproducible method for their generation as well as the induction of irreversible suppressive function. Based on lessons learned from the use of DCs as tools in clinical vaccine trials in cancer, we discuss the unknown aspects and risks of DC therapy in transplantation.

Evaluation of penile rigidity with color Doppler flow imaging in Chinese patients with erectile dysfunction.

OBJECTIVES: To assess the role of color Doppler flow imaging (CDFI) in the evaluation of Chinese patients with erectile dysfunction (ED) and to explore the association between penile rigidity and hemodynamic parameters of CDFI. METHODS: Totally 74 ED patients with an age range of 22-69 (median age 47) were included in our study, hemodynamic parameters including the peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) of the penile cavernous artery were measured by CDFI before and after intracavernous pharmacological testing. The degree of penile rigidity was classified according to Schramek grading system. The correlation between the penile rigidity state and its hemodynamic parameters was analyzed. RESULTS: In ED patients, the abnormalities of cavernous artery and dorsal vein could be evaluated by the value of PSV and EDV with combination of penile rigidity. Among different penile rigidity status, the PSV, EDV and RI of the cavernous artery were significantly different (p < 0.05). The RI correlated significantly with the penile rigidity (r(2) = 0.7948). CONCLUSION: The CDFI hemodynamics of the penile cavernous artery are helpful in the etiological diagnosis of Chinese ED patients and can be used as one of the quantitative indexes for penile rigidity, which is consistent with western guidelines.

[Value of transrectal ultrasonography in the diagnosis of midline prostatic cysts].

OBJECTIVE: To assess the value of transrectal ultrasonography (TRUS) in the diagnosis of midline prostatic cysts. METHODS: We retrospectively analyzed the TRUS manifestations of 87 cases of midline prostatic cysts. RESULTS: Of the total number, 33 cases were diagnosed as Müllerian duct cysts, 21 cases ejaculatory duct cysts and the other 33 cases undifferentiated midline prostatic cysts; 19 cases had dilated seminal vesicles, 19 seminal vesicle agenesis, 9 seminal vesiculitis and 5 dilation of the ejaculatory duct. CONCLUSION: TRUS, convenient, sensitive, safe and non-invasive, is a desirable method for the diagnosis of midline prostatic cysts.

[Testicular microlithiasis influences seminal profile and testicular blood flow in infertile men].

OBJECTIVE: To investigate the testicular blood flow in patients with testicular microlithiasis (TM) and its correlation with the seminal profile in infertile men. METHODS: We selected 88 infertile men and examined them by testicular color Doppler and routine seminal tests. RESULTS: Testicular microlithiasis was found in 19 (19.3%) of the patients, classic testicular microlithiasis (CTM) in 7 (8.0%), and limited testicular microlithiasis (LTM) in 10 (11.3%). No significant differences were observed in the age of onset, bilateral testicular volume, resistance index (RI) of bilateral testicular arteries, semen amount and the rate of teratospermia. The bilateral testicular peak systolic velocity (PSV), sperm count and sperm motility were significantly lower in the CTM than in the LTM group (P < 0.05), but showed no statistically significant difference between the LTM and the non-calcification group. CONCLUSION: TM may be one of the causes of poor sperm function in infertile men.

Outcome of implanting penile prosthesis for treating erectile dysfunction: experience with 42 cases.

AIM: To report a short-time result of three-piece inflatable penile prosthesis (IPP) implantation on treating patients with organic erectile dysfunction (ED). METHODS: Three-piece IPPs were implanted in 42 Chinese patients with ED refractory to systemic treatment between May 2002 and May 2004. The etiologies of ED were neurogenic (28 with paraplegia and seven with traumatic nervi-erigentes injury); congenital venous leakage (5 cases), fibrosis of corpus cavernosum (1case) and Klinefelter's syndrome (1 case). The follow-up period ranged from 24 to 57 months. RESULTS: Implantation procedures were successfully performed upon all 42 patients. The length of implanted prosthesis was from 13 cm to 18 cm, and the diameter was 1 cm. The implanted prosthesis was made by the Medical Instrumentation Company of Muping (Muping, Shandong, China). Localized infection occurred in only one patient and mechanical complications occurred in five patients. Coitus could be performed in 41 cases (97.6%). Three patients with congenital venous leakage made their spouses pregnant after implantation. CONCLUSION: Implantation of three-piece IPP is an effective and safe modality for treating patients with ED. It can be well accepted by Chinese patients because of its efficacy.

Ex vivo perfusion with mitomycin C containing solution prolongs heart graft survival in rats.

Mitomycin C (MMC) is an alkylating agent which suppresses allogeneic T-cell responses. We analyzed the effect of graft perfusion with MMC on transplant survival. Hearts from Brown-Norway (BN) rats were perfused ex vivo with MMC-containing solution, stored and implanted into Lewis (LEW) rats. In order to analyze the in vivo effect of MMC, recipients received MMC posttransplantation or were pretreated with MMC-incubated donor-derived peripheral blood mononuclear cells (PBMCs). The results show that MMC-perfusion significantly prolongs graft survival. Treatment of recipients with MMC has no effect, whereas MMC-treated donor PBMCs injected into the recipient prolong graft survival. Our findings indicate that the targeted perfusion of donor hearts with MMC-containing solution protects the graft from rejection.

Vasculogenic Mimicry in Prostate Cancer: The Roles of EphA2 and PI3K.

BACKGROUND: Aggressive tumor cells can form perfusable networks that mimic normal vasculature and enhance tumor growth and metastasis. A number of molecular players have been implicated in such vasculogenic mimicry, among them the receptor tyrosine kinase EphA2, which is aberrantly expressed in aggressive tumors. Here we study the role and regulation of EphA2 in vasculogenic mimicry in prostate cancer where this phenomenon is still poorly understood. METHODS: Vasculogenic mimicry was characterized by tubules whose cellular lining was negative for the endothelial cell marker CD34 but positive for periodic acid-Schiff staining, and/or contained red blood cells. Vasculogenic mimicry was assessed in 92 clinical samples of prostate cancer and analyzed in more detail in three prostate cancer cell lines kept in three-dimensional culture. Tissue samples and cell lines were also assessed for total and phosphorylated levels of EphA2 and its potential regulator, Phosphoinositide 3-Kinase (PI3K). In addition, the role of EphA2 in vasculogenic mimicry and in cell migration and invasion were investigated by manipulating the levels of EphA2 through specific siRNAs. Furthermore, the role of PI3K in vasculogenic mimicry and in regulating EphA2 was tested by application of an inhibitor, LY294002. RESULTS: Immunohistochemistry of prostate cancers showed a significant correlation between vasculogenic mimicry and high expression levels of EphA2, high Gleason scores, advanced TNM stage, and the presence of lymph node and distant metastases. Likewise, two prostate cancer cell lines (PC3 and DU-145) formed vasculogenic networks on Matrigel and expressed high EphA2 levels, while one line (LNCaP) showed no vasculogenic networks and lower EphA2 levels. Specific silencing of EphA2 in PC3 and DU-145 cells decreased vasculogenic mimicry as well as cell migration and invasion. Furthermore, high expression levels of PI3K and EphA2 phosphorylation at Ser897 significantly correlated with the presence of vasculogenic mimicry and in vitro inhibition of PI3K by LY294002 disrupted vasculogenic mimicry, potentially through a reduction of EphA2 phosphorylation at Ser897. CONCLUSIONS: The expression levels of PI3K and EphA2 are positively correlated with vasculogenic mimicry both in vivo and in vitro. Moreover, phosphorylation levels of EphA2 regulated by PI3K are also significantly associated with vasculogenic mimicry in vivo. Based on its functional implication in vasculogenic mimicry in vitro, EphA2 signaling may be a potential therapeutic target in advanced prostate cancer.

Matrix metalloproteinase-9 is required for vasculogenic mimicry by clear cell renal carcinoma cells.

BACKGROUND: Vasculogenic mimicry (VM), a new pattern of tumor microcirculation system, has been proved to be important for tumor growth and progression and may be one of the causes of antiangiogenesis resistance. Matrix metalloproteinase-9 (MMP9) was shown to correlate with VM formation in some other cancers. However, the relationship between VM formation and MMP9 in renal cell carcinoma (RCC) has not been determined. METHODS: The VM formation and MMP9 expressions were analyzed by CD34/periodic acid-Schiff dual staining and immunohistochemistry in 119 RCC specimens. We used a well-established 3-dimention culture model to compare VM formation in 786-O, 769-P, and HK-2 cell lines in vitro. MMP9 expressions on either messenger RNA or protein levels were compared among the cell lines by quantitative polymerase chain reaction or Western blot. To determine further the relationship between MMP9 and VM in RCC, 786-O and 769-P were treated with specific MMP9 inhibitor or small interfering RNA. VM formation, cell migration, and invasion were subsequently assessed by 3-dimention culture, wound-healing, and transwell assays. RESULTS: Immunohistochemistry demonstrated both VM formation and MMP9 overexpression were positively associated with clinical staging, pathological grade, and metastasis (P<0.01). VM formation was closely correlated with MMP9 overexpression in RCC (r = 0.602, P<0.01). Lower MMP9 expression level was observed in normal kidney cell line HK-2, which was unable to form VM on Matrigel, whereas higher expression of MMP9 was found in VM-forming cancer cell lines 786-O and 769-P. Inhibition of MMP9 not only disrupted VM formation in 786-O and 769-P but also reduced cell migration and invasion. CONCLUSIONS: These results indicate an intimate relationship between MMP9 overexpression and VM formation in RCC. Treatments targeting VM formation by inhibiting the activity of MMP9 could be beneficial in RCC therapy.

The performance of transrectal ultrasound in the diagnosis of seminal vesicle defects: a comparison with magnetic resonance imaging.

Obstructive azoospermia (OA) is one of the most common causes of male infertility. Transrectal ultrasound (TRUS) has been used to diagnose OA for many years. From 2009 to 2013, we evaluated a prospective cohort of 1249 patients with suspected OA using TRUS. It was found that dilation of the ejaculatory duct (ED) (29.9%, 374/1249) was the most common cause of OA, followed by seminal vesicle (SV) abnormalities (28.5%, 356/1249). A total of 237 patients were diagnosed with congenital defects (agenesis and/or hypoplasia) of the SV, constituting more than half of the cases of SV disease in OA (19.0%, 237/1249). In contrast to ED, congenital defects of the SV could not be corrected with surgical treatment. Therefore, it is meaningful to compare TRUS and magnetic resonance imaging (MRI) for accurate diagnosis of SV defects. Among our patients, 30 with agenesis or/and hypoplasia of the SV on TRUS were further evaluated using pelvic MRI within 2 years, with the objective of verifying the TRUS results. The concordance rate for diagnosing congenital defects of the SV was 73.3% (22/30). We concluded that TRUS is a reliable and convenient method for diagnosing agenesis or hypoplasia of the SV in OA patients with a high concordance with MRI while MRI is useful in patients with inconclusive TRUS findings.

Association of DSC3 mRNA down-regulation in prostate cancer with promoter hypermethylation and poor prognosis.

BACKGROUND: Desmocollin 3 (DSC3), a member of the cadherin gene superfamily, is associated with pathogenesis of some cancers, but its role in prostate cancer (PCa) remains largely unknown. METHODS: DSC3 gene expression level in available PCa microarray dataset was examined using the Oncomine database. DSC3 transcript expression in prostate cell line panel and an independent tissue cohort (n = 52) was estimated by quantitative PCR (Q-PCR). Epigenetic status of DSC3 gene promoter in PCa was investigated by uploading three dataset (ENCODE Infinium 450K array data and two methylation sequencing) in UCSC genome browser. While pyrosequencing analysis measured promoter DNA methylation, Q-PCR estimates were obtained for DSC3 transcript re-expression after 5-Aza-deoxycytidine (5-Aza) treatment. Clinical relevance of DSC3 expression was studied by Kaplan-Meier survival analysis. Finally, functional studies monitoring cell proliferation, migration and invasion were performed in prostate cell lines after siRNA mediated DSC3 knockdown or following 5-Aza induced re-expression. EMT markers Vimentin and E-cadherin expression was measured by Western Blot. RESULTS: Microarray data analyses revealed a significant decrease in DSC3 transcript expression in PCa, compared to benign samples. Q-PCR analysis of an independent cohort revealed DSC3 transcript down-regulation, both in PCa cell lines and tumor tissues but not in their benign counterpart. Examination of available NGS and Infinium data identified a role for epigenetic regulation DSC3 mRNA reduction in PCa. Pyrosequencing confirmed the increased DSC3 promoter methylation in cancer cell lines and restoration of transcript expression upon 5-Aza treatment further corroborated this epigenetic silencing mechanism. Importantly Kaplan-Meier analysis of an outcome cohort showed an association between loss of DSC3 expression and significantly increased risk of biochemical recurrence. Functional studies indicate a role for epithelial-mesenchymal transition in DSC3 regulated cell migration/invasion. CONCLUSION: Taken together, our data suggests that DNA methylation contributes to down-regulation of DSC3 in prostate cancer, and loss of DSC3 predicts poor clinical outcome.