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Background Cancer treatment remains one of the most formidable challenges worldwide. Some novel treatment strategies, including molecularly targeted therapy, gene therapy, and cellular immunotherapy, have also been investigated to improve therapeutic effects for cancer patients and have demonstrated unexpected positive effects. This systematic review and meta-analysis evaluated the efficacy and safety of oncolytic virus (OV) monotherapy or combination therapy for intermediate to advanced solid tumors. Methods We retrieved articles from PubMed, Embase, Web of Science, CNKI, Wanfang and VIP. The quality of the included studies was assessed by Review Manager Software version 5.3. STATA software was used to perform meta-analyses of efficacy, overall survival (OS) and adverse reactions. Results A total of 22 studies involving 3,996 patients were included in this analysis, including 13 H101 studies, 5 T-VEC studies, 2 Pexa-Vec studies, 1 HF10 study and 1 Reolysin study. Regarding oncolytic adenovirus H101, meta-analysis showed that patients treated with H101 monotherapy or H101 combined with chemotherapy had a significantly higher objective response rate (ORR) than those treated with chemotherapy. Patients in the H101 and T-VEC groups had significantly longer effect size (ES) than the control group patients. The odds ratio (OR) and ES of patients with hepatocellular carcinoma, lung cancer and melanoma treated with OV were analyzed. For the safety profile, the total incidence of adverse reactions was similar in both groups. In terms of the other OVs, according to a systematic review, we found that after Reolysin treatment, the ORR was 26.9% in patients with head and neck cancer. The phase I study of HF10 exhibited some therapeutic potential. The adverse events (AEs) associated with the other OVs mainly included fever, nausea and vomiting, leukopenia, and hypotension. Discussion OVs are effective and well tolerated for the treatment of intermediate to advanced solid cancer and represent a promising therapeutic approach for solid cancers.

Prostate cancer (PCa) is a leading adult malignant tumor. Recent research has shown that speckle-type BTB/POZ protein (SPOP) mutant is the top frequently mutated gene in PCa, which makes it an important biomarker. In this paper, we aimed at identifying critical genes and pathways related to SPOP mutation in PCa. Recent The Cancer Genome Atlas data showed that 12% of patients with PCa were SPOP mutant. There were 1,570 differentially expressed genes, and online enrichment analysis showed that these genes were mainly enriched in metabolism, pathways in cancer and reactive oxygen species. INS, GNG13, IL6, HTR5A, SAA1, PPY, CXCR5, CXCL13, CD19 and CCL20 were identified as hub genes. The lower SPOP expression level was associated with poor prognosis. In all, our findings showed that various pathways and genes could play critical roles in SPOP mutation in PCa, providing potential options for individualized treatment.

Prostate cancer is still one of the most common malignancies in men all around the world. The mechanism of how prostate cancer initiates and develops is still not clear. Here in this study, we show that tumor suppressor ZBTB38 could suppress the migration and proliferation of prostate cancer cells. We find lower ZBTB38 expression in prostate cancer tissues, which also strongly predicts a poorer prognosis of prostate cancer. ZBTB38 binds DKK1 (Dickkopf WNT signaling pathway inhibitor 1) locus and promotes DKK1 expression in prostate cancer cell lines. Consistently, reduction of DKK1 expression significantly restores ZBTB38-mediated suppression of migration and proliferation of prostate cancer cell lines. Mechanistically, we find that ZBTB38 primarily binds the promoters of target genes, and differentially regulates the expression of 1818 genes. We also identify PRKDC (protein kinase, DNA-activated, catalytic subunit) as a ZBTB38-interacting protein that could repress the function of ZBTB38 in suppressing migration and proliferation of prostate cancer cells. Taken together, our results indicate that ZBTB38 could repress cell migration and proliferation in prostate cancer via promoting DKK1 expression, and also provide evidence supporting ZBTB38 as a potential prognosis marker for prostate cancer.

BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) is the lethal stage of prostate cancer and the main cause of morbidity and mortality, which is also a potential target for immunotherapy. METHOD: In this study, using the Approximate Relative Subset of RNA Transcripts (CIBERSORT) online method, we analysed the immune cell abundance ratio of each sample in the mCRPC dataset. The EdgeR (an R package) was used to classify differentially expressed genes (DEGs). Using the Database for annotation, visualisation and interactive exploration (DAVID) online method, we performed functional enrichment analyses. STRING online database and Cytoscape tools have been used to analyse protein-protein interaction (PPI) and classify hub genes. RESULTS: The profiles of immune infiltration in mCRPC showed that Macrophages M2, Macrophages M0, T cells CD4 memory resting, T cells CD8 and Plasma cells were the main infiltration cell types in mCRPC samples. Macrophage M0 and T cell CD4 memory resting abundance ratios were correlated with clinical outcomes. We identified 1102 differentially expressed genes (DEGs) associated with the above two immune cells to further explore the underlying mechanisms. Enrichment analysis found that DEGs were substantially enriched in immune response, cell metastasis, and metabolism related categories. We identified 20 hub genes by the protein-protein interaction network analysis. Further analysis showed that three critical hub genes, CCR5, COL1A1 and CXCR3, were significantly associated with prostate cancer prognosis. CONCLUSION: Our findings revealed the pattern of immune cell infiltration in mCRPC, and identified the types and genes of immune cells correlated with clinical outcomes. A new theoretical basis for immunotherapy may be given by our results.

Metastatic castration-resistant prostate cancer (mCRPC) is the lethal stage and the leading cause of death in prostate cancer patients, among which bone metastasis is the most common site. Here in this article, we downloaded the gene expression data and clinical information from online dataset. We found that prostate cancer metastasis in bone is prone to have higher prostate-specific antigen (PSA) and longer time on first-line androgen receptor signaling inhibitors (ARSI). A total of 1,263 differentially expressed genes (DEGs) were identified and results of functional enrichment analysis indicated the enrichment in categories related to cell migration, cancer related pathways and metabolism. We identified the top 20 hub genes from the PPI network and analyzed the clinical characteristics correlated with these hub genes. Finally, we analyzed the immune cell abundance ratio of each sample in different groups. Our results reveal the different clinical characteristics, the immune cell infiltration pattern in different sites of mCRPC, and identify multiple critical related genes and pathways, which provides basis for individualized treatment.

Prostate cancer is the most common malignancy in men in developed countries. In previous study, we identified HNF1B (Hepatocyte Nuclear Factor 1β) as a downstream effector of Enhancer of zeste homolog 2 (EZH2). HNF1B suppresses EZH2‐mediated migration of two prostate cancer cell lines via represses the EMT process by inhibiting SLUG expression. Besides, HNF1B expression inhibits cell proliferation through unknown mechanisms. Here, we demonstrated that HNF1B inhibited the proliferation rate of prostate cancer cells. Overexpression of HNF1B in prostate cancer cells led to the arrest of G1 cell cycle and decreased Cyclin D1 expression. In addition, we re‐explored data from ChIP‐sequencing (ChIP‐seq) and RNA‐sequencing (RNA‐seq), and demonstrated that HNF1B repressed Cyclin D1 via direct suppression of SMAD6 expression. We also identified CDKN2A as a HNF1B‐interacting protein that would contribute to HNF1B‐mediated repression of SMAD6 expression. In summary, we provide the novel mechanisms and evidence in support HNF1B as a tumour suppressor gene for prostate cancer.

In this paper, the difference between the fabric features of the cloth and the normal part is used to realize the automatic detection of the flaws in the cloth. And the Gabor filtering method and support vector machine (SVM) classifier are used to detect the flaws. The detection mainly includes two steps. The first step is to divide the cloth image into multiple sub-blocks of the same size, each sub-block as a sample, and then calculate the texture features of each sub-block separately, and the second step uses SVM classifier to different the samples of cloths. In the second step, the SVM classifier is used to classify different cloth samples to detect the fabric defects. Experiments show that the proposed algorithm can basically realize the automatic detection function of flaws in the cloth and can effectively identify whether the cloth has flaws.

Ensuring food quality and safety is one of the important tasks of food production enterprises. In this paper, a foreign body recognition method based on Support Vector Machine (SVM) for food image is proposed. Firstly, the X-ray image of food is segmented by automatic threshold method, and then the feature is extracted and classified. The simulation results show that compared with BP neural network and K-nearest neighbor algorithm, SVM algorithm has better stability and more effective accuracy to realize the classification.

Empirical natural language processing (NLP) systems in application domains (e.g., healthcare, finance, education) involve interoperation among multiple components, ranging from data ingestion, human annotation, to text retrieval, analysis, generation, and visualization. We establish a unified open-source framework to support fast development of such sophisticated NLP workflows in a composable manner. The framework introduces a uniform data representation to encode heterogeneous results by a wide range of NLP tasks. It offers a large repository of processors for NLP tasks, visualization, and annotation, which can be easily assembled with full interoperability under the unified representation. The highly extensible framework allows plugging in custom processors from external off-the-shelf NLP and deep learning libraries. The whole framework is delivered through two modularized yet integratable open-source projects, namely Forte (for workflow infrastructure and NLP function processors) and Stave (for user interaction, visualization, and annotation).

Aim: BAP1 is frequently mutated in clear cell renal cell carcinoma (ccRCC) with a definitive role still unclear. Methods: In silico analysis of BAP1-mutant and wild-type gene enrichment and functional annotation in TCGA-KIRC dataset was performed. Target gene was studied based on functional clustering and was knowledge-based. Validation using in-house pathological sections were performed immunohistochemically. In vitro and in vivo studies on target gene were performed. Results: The TCGA ccRCC dataset included 534 ccRCC samples. BAP1 was frequently mutated and more frequently downregulated in ccRCC compared to normal kidney tissue or benign renal tumors. In the analysis between samples with BAP1 mutation (N = 33) and pan-negative (N = 33), we found that cancers with BAP1 mutation was significantly enriched for 14 pathways, of which 3 were DNA repair pathways, in which EZH2 played a role. CcRCC patients with lower BAP1 expression had poor prognosis and showed higher EZH2 expression, which also conferred worsened survival. Genetic and pharmaceutical inhibition of EZH2 not only inhibited BAP1-mutatn ccRCC cell viability and invasion but also abrogated genetic replenishing of BAP1 expression. Validation cohort encompassing 62 ccRCC samples confirmed the worsened phenotype for cases with higher EZH2 expression and significant positive correlation between expressions of EZH2 and BAP1. EZH2 inhibitor also inhibited tumor growth in xenograft mouse model with BAP1-mutated ccRCC cells with unremarkable toxicity. Conclusion: CcRCC with decreased BAP1 level has poor prognosis and is associated with higher EZH2 expression. Inhibition of EZH2 in BAP1-mutated entity holds promise for further investigation.

Aim Clear-cell renal cell carcinoma (ccRCC) is characterized with underlying genetic disorders and the role of low density lipoprotein receptor-related protein 1 (LRP1) in ccRCC is unknown. Method An in silico exploratory analysis using multiple public genetic datasets was used to establish association between LRP1 expression and clinicopathological parameters. Associations of interest were validated using 155 ccRCC samples using immunohistochemistry. Results LRP1 was overexpressed in tumor compared with normal kidney tissue. Increased LRP1 expression in ccRCC was associated with advanced stage, grade and worsened overall survival and progression-free survival. Functional annotation indicated an immune-modulatory role of LRP1 in ccRCC. LRP1 expression was significantly correlated with expressions of PBRM1, SETD2, and KDM5C. Positive correlations between LRP1 and pro-angiogenic factors ERAP1, SCG2, STAB1, and RUNX1 were observed. LRP1 expression was positively correlated with PD-L2 level. Negative correlations between LRP1 and anti-angiogenic factors EMCN and IL18 were observed. LRP1 expression was not associated with microvessel density (MVD) yet was negatively correlated with tumor-infiltrating lymphocytes (TIL). Conclusion LRP1 is associated with worsened prognosis in ccRCC and is related to cancer immune modulation. LRP1-targeted therapy can be of therapeutic potential.

Shenghua Liu,1,2,* Guanxiong Ding,1,2,* Zhongwen Zhou,1,2 Chenchen Feng1,2 1Department of Urology, Huashan Hospital, Shanghai, China; 2Fudan Institute of Urology, Shanghai, China *These authors contributed equally to this work Aim: Adrenocortical carcinoma (ACC) is characterized by overexpressed CTNNB1, which is reported to modulate immune exclusion. Cross talk between CTNNB1 and cancer immunity in ACC remains unclear. Materials and methods: In silico reproduction of TCGA-ACC dataset (N = 92) and external validation using tissue samples were performed (N = 16). Expression data of CTNNB1, PD-1, and PD-L1 were extracted in silico and tumor-infiltrating lymphocytes (TILs) were profiled using code provided by Tumor IMmune Estimation Resource (TIMER). In-house formalin-fixed paraffin-embedded ACC samples were processed using immunohistochemical (IHC) staining for CTNNB1, CD45, PD-1, and PD-L1. Results: Increased CTNNB1 expression was significantly associated with worsened overall survival (OS) (P = 0.006). CD8+ cells were significantly associated with better OS (P = 0.02). Higher PD-L1 (P = 0.019), but not PD-1 expression (P = 0.325), was associated with better OS. CTNNB1 overexpression was significantly associated with increased tumor purity (r = 0.356, P = 0.002) and fewer TILs (r = -0.833, P = 0.029), decreased infiltrating CD8+ cells (P = 0.033), and increased infiltrating B cells (P = 0.026). CTNNB1 expression was negatively correlated with PD-L1 expression (r = -0.308, P = 0.006) but not with PD-1 expression (P = 0.067), which were externally validated (P = 0.032 for PD-L1 and P = 0.400 for PD-1). The Cox regression model encompassing gender, B cells, CD8+ cells, PD-L1, CTNNB1, and Ki-67 revealed that only Ki-67 overexpression remained significantly associated with OS (P < 0.001), while CTNNB1 showed marginal significance (P = 0.06). CTNNB1-overexpressed patients were more likely to have cortisol excess (P = 0.003). Conclusion: ACC with CTNNB1 overexpression is associated with poor prognosis and decreased immunity. Our findings suggest that CTNNB1-targeting therapy may overcome immune exclusion in ACC. Keywords: adrenocortical carcinoma, CTNNB1, tumor-infiltrating lymphocyte, PD-L1, prognosis

Objectives: To analyze the correlation between pharmacogenomic biomarkers and the efficacy of pirarubicin (THP, also named 4’-O-tetrahydropyranyl-adriamycin) and to explore potential associations of individual genetic backgrounds with the clinical outcomes of non-muscle-invasive bladder cancer (NMIBC) patients. Methods: Between July 2003 and June 2011, a total of 91 patients were treated with transurethral resection (TUR) of the bladder tumor and were histopathologically confirmed to have NMIBC. Patients received an immediate instillation and maintenance therapy with THP. All patients underwent follow-up for recurrence. We genotyped 13 single nucleotide polymorphisms (SNPs) from blood and saliva DNA samples of all patients. Results: The associations of patients’ genotypes with tumor recurrence risks were analyzed by survival analysis. A total of 16 (17.6%) of the 91 patients with NMIBC had tumor recurrences with a median follow-up of 17 months (range, 2–83 months). We confirmed the effect of the European Organization for Research and Treatment of Cancer (EORTC) risk score for predicting tumor recurrence (p = 0.002, log-rank test). We adjusted for the EORTC score and found that 2 SNPs, NOS3 895G>T (rs1799983) (p = 0.02, HR = 4.32, 95% CI, 1.30–14.39, GT+TT vs. GG) and CBR3 730G>A (rs1056892) (p = 0.04, HR = 2.57, 95% CI, 1.07–6.18, GA+AA vs. GG), were significantly associated with a higher recurrence risk after TUR and instillations of THP in NMIBC patients. Conclusions: Our results suggest that NOS3 895G>T and CBR3 730G>A are genetic markers that can be used to predict tumor recurrence in NMIBC patients receiving intravesical instillations of THP. The effects of those 2 SNPs are independent of the EORTC scores. Further studies with larger sample sizes and longer follow-ups are needed to confirm our results.

// Guanxiong Ding 1, 2, * , Shenghua Liu 1, 2, * , Qiang Ding 1, 2 and Chenchen Feng 1, 2 1 Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, PR China 2 Fudan Institute of Urology, Fudan University, Shanghai 200040, PR China * These authors contributed equally to this work Correspondence to: Chenchen Feng, email: drfengchenchen@163.com Keywords: adrenocortical carcinoma; HSD17B4; tumor suppressor; p53 Received: January 25, 2017 Accepted: November 07, 2017 Published: December 01, 2017 ABSTRACT Aim: Adrenocortical carcinoma (ACC) is characterized with excessive hormone production. We therefore investigated expression of hormone-related genes in ACC. Results: We queried status of 14 key genes directly involved in adrenal hormone production and found HSD17B4 expression was upregulated in 39% of ACC cases on top of all queried genes. Overexpression of HSD17B4 was significantly associate with a normo-hormonal phenotype. Constitutive HSD17B4 expression was higher in ACC cell line NCI-H295R than in adrenocortical small cell carcinoma cell line SW13. NCI-H295R cells with HSD17B4-knockdown (KD) demonstrated significantly inhibited proliferation, increased apoptosis, and increased cell cycle arrest. Enrichment analysis for mRNA expression in ACC samples with or without HSD17B4 overexpression showed significant change in p53 pathway. Replenish of HSD17B4 in SW13 cells and knockdown of HSD17B4 in H295R cells confirmed alterations in MDM4, ATR, and IE24 with alterations more contrasting in H295R cells. HSD17B4-KD inhibited cell invasion, migration and anchorage independent growth of NCI-H295R cells, but not of SW13 cells. Materials and Methods: Clinical and genetic data of ACC samples were reproduced from the ACC dataset of The Cancer Genome Atlas (TCGA) database using cBioPortal. Genes participating in adrenal hormone production were queried. Association between gene status and hormone release were studied and in vitro assays using RNA interference were carried out. Conclusions: Overexpression of HSD17B4 exerted tumor suppressive function in adrenocortical carcinoma and was not related to hormone excess. Crosstalk between HSD17B4 and p53 warrants further investigation.

Prostate cancer is the most common malignancy in men in developed countries. Overexpression of enhancer of zeste homolog 2 (EZH2), the major histone H3 lysine 27 methyltransferase, has been connected to prostate cancer malignancy. However, its downstream genes and pathways have not been well established. Here, we show tumor suppressor Hepatocyte Nuclear Factor 1β (HNF1B) as a direct downstream target of EZH2. EZH2 binds HNF1B locus and suppresses HNF1B expression in prostate cancer cell lines, which is further supported by the reverse correlation between EZH2 and HNF1B expression in clinical samples. Consistently, restored HNF1B expression significantly suppresses EZH2-mediated overgrowth and EMT processes, including migration and invasion of prostate cancer cell lines. Mechanistically, we find that HNF1B primarily binds the promoters of thousands of target genes, and differentially regulates the expression of 876 genes. We also identify RBBP7/RbAP46 as a HNF1B interacting protein which is required for HNF1B-mediated repression of SLUG expression and EMT process. Importantly, we find that higher HNF1B expression strongly predicts better prognosis of prostate cancer, alone or together with lower EZH2 expression. Taken together, we have established a previously underappreciated axis of EZH2-HNF1B-SLUG in prostate cancer, and also provide evidence supporting HNF1B as a potential prognosis marker for metastatic prostate cancer.

To analyze the correlation between pharmacogenomic biomarkers and the efficacy of pirarubicin (THP, also named 4'-O-tetrahydropyranyl-adriamycin) and to explore potential associations of individual genetic backgrounds with the clinical outcomes of non-muscle-invasive bladder cancer (NMIBC) patients.Between July 2003 and June 2011, a total of 91 patients were treated with transurethral resection (TUR) of the bladder tumor and were histopathologically confirmed to have NMIBC. Patients received an immediate instillation and maintenance therapy with THP. All patients underwent follow-up for recurrence. We genotyped 13 single nucleotide polymorphisms (SNPs) from blood and saliva DNA samples of all patients.The associations of patients' genotypes with tumor recurrence risks were analyzed by survival analysis. A total of 16 (17.6%) of the 91 patients with NMIBC had tumor recurrences with a median follow-up of 17 months (range, 2-83 months). We confirmed the effect of the European Organization for Research and Treatment of Cancer (EORTC) risk score for predicting tumor recurrence (p = 0.002, log-rank test). We adjusted for the EORTC score and found that 2 SNPs, NOS3 895GT (rs1799983) (p = 0.02, HR = 4.32, 95% CI, 1.30-14.39, GT+TT vs. GG) and CBR3 730GA (rs1056892) (p = 0.04, HR = 2.57, 95% CI, 1.07-6.18, GA+AA vs. GG), were significantly associated with a higher recurrence risk after TUR and instillations of THP in NMIBC patients.Our results suggest that NOS3 895GT and CBR3 730GA are genetic markers that can be used to predict tumor recurrence in NMIBC patients receiving intravesical instillations of THP. The effects of those 2 SNPs are independent of the EORTC scores. Further studies with larger sample sizes and longer follow-ups are needed to confirm our results.

BACKGROUND Metastasis is the primary cause of prostate cancer (PCa) lethality and poses a huge clinical obstacle. Lipocalin 2 (LCN2), a member of the lipocalin family, is aberrantly expressed in some human cancers and has been implicated in the progression of some tumors. However, the role of LCN2 in the metastatic capacity of prostate cancer (PCa) is poorly understood. METHODS LCN2 expression was examined by RT-qPCR and/or immunoblotting in human prostate tissue specimens and prostate cancer cell lines LNCaP, C4-2, 22RV1, PC3, DU-145, and PC3MM2. LCN2 protein level in human serum samples was determined by ELISA. Lentiviruses-mediated over-expression of LCN2 and knockdown of LCN2 was conducted to evaluate the role of LCN2 in cell migratory and invasive capacities of prostate cancer cells. Cell migration and invasion was examined by transwell chamber assay. Knockdown of SLUG by lentivirus was performed to investigate its role in LCN2-promoted cell migration and invasion in vitro (22RV1 cell line) and metastasis in vivo (tail vein metastasis assay in nude mice). Role of ERK signaling in LCN2-mediated up-regulation of SLUG was assayed by using ERK inhibitor U0126. RESULTS We confirmed that LCN2 levels were correlated positively with invasive prostate cancer in human tissue and serum samples, and were also consistently associated with the invasive capacity of prostate cancer cell lines. The over-expression of LCN2 in 22RV1 cells (not highly invasive) promoted the epithelial–mesenchymal transition (EMT), increasing cell motility and invasiveness, while the knockdown of LCN2 in PC3 cells (highly invasive) inhibited EMT, decreasing cell motility and invasiveness. Among the multiple EMT transcription factors, LCN2 specifically induces the expression of SLUG, which was shown here to be required for the LCN2-induced increase in the invasive capacity of prostate cancer cells both in vitro and in vivo. Mechanistically, LCN2 promoted SLUG expression via activating ERK signaling pathway. CONCLUSION LCN2 plays an important role in promoting cell migration and invasion of prostate cancer by inducing EMT through the ERK/SLUG axis. Therefore, targeted inhibition of LCN2 may represent a therapeutic strategy to prevent the metastasis of prostate cancer. Prostate 75:957–968, 2015. © 2015 Wiley Periodicals, Inc.

Renal clear cell carcinoma (ccRCC) is characterized by frequent mutation in SETD2, which has recently been shown to regulate mismatch repair (MMR). We aim to investigate the association between MMR machinery genes and SETD2 mutation in ccRCC. We exploited the Genomics of Drug Sensitivity in Cancer (GDSC) database to identify selective inhibitors for SETD2 mutant ccRCC cells. We also exploited the Cancer Genome Atlas (TCGA) database to study the association between SETD2 status and MMR-related genes. In vitro studies were performed to validate the in silico findings. Reproduction of the GDSC database revealed four compounds with significant selectivity for SETD2 mutant ccRCC cells, amongst which two compounds targeted PI3Kβ. Phosphorylation of AKT at both S473 and T308 was decreased following PI3Kβ inhibitor treatment in SETD2 mutant ccRCC cells, whereas the basal pAKT level was not changed between mutant and wild-type SETD2. Both decreased MLH1 and increased AKT levels induced lower PMS2, indicating that MMR was mediated by SETD2 via both AKT and MLH1 in ccRCC. Analysis of the TCGA database further revealed high tendency of homozygous co-deletion of SETD2 and MLH1. In the absence of MLH1, suppression of pAKT by PI3Kβ inhibitor was mitigated and inhibition in cell proliferation, invasiveness, migratory ability and tumourigenesis was partially restored. Besides the reported H3K36-trimethylation pathway, we found that SETD2 mutation also mediated MMR via AKT-induced PMS2 decrease and co-loss of MLH1 loss in ccRCC.

Prostate cancer is the most commonly diagnosed malignancy and is the second leading deadly reason among male cancer. WDFY2, which is found to be a cancer-specific fusion gene with CDKN2D in ovarian cancer, is a new gene with unknown function in carcinogenesis. In this study, we investigated the role of WDFY2 in prostate cancer development. We examined WDFY2 expression in human prostate tissue specimens and prostate cancer cell lines BPH-1, LNCaP, PC3, and DU-145. Overexpression of WDFY2 was performed to evaluate the role of WDFY2 in cell proliferation, migration, and colony formation of prostate cancer cells. We analyzed the clinical impact and prognosis of WDFY2 expression on the progress of prostate cancer through data from online datasets. Our results showed that WDFY2 had lower expression level in prostate tumors than in normal tissues. Overexpression of WDFY2 in prostate cancer cells DU145 and PC-3 led to the suppression of cancer cell migration and colony formation. Furthermore, we found that WDFY2 exerted its role by suppressing the activity of Akt pathway other than the epithelial–mesenchymal transition progression. In conclusion, we have uncovered WDFY2 as a tumor suppressor gene and a new potential biomarker for cancer progression. Our results showed that WDFY2 inhibited cancer cell colony formation and migration via suppressing Akt pathway, making it a potential new therapeutic target in prostate cancer.

In this study, we aimed to validate the association of 8 reported significant loci at 5q35.3, 7p14.3, 13q14.1 and 16p12.3 with urolithiasis in Chinese Han population. We performed case-control association analysis using 624 patients with nephrolithiasis and 1008 control subjects. We selected single-nucleotide polymorphism (SNPs) including rs12654812 and rs11746443 from 5q32.3; rs12669187 and rs1000597 from 7q14.3; rs7981733, rs4142110 and rs17646069 from 13q14.1 and rs4293393 from 16p12.3 which were previously reported to be associated with nephrolithiasis. We found none of these eight reported SNPs were significant associated with urolithiasis risk in Chinese Han population, which suggested that differences could exist in the mechanisms of calcium urolithiasis between Chinese and Japanese Ethnics. The A allele of rs12669187 was significantly correlated with increased level of serum magnesium. The C allele of rs1000597 was associated with higher levels of serum creatinine, uric acid, calcium and lower urine pH level. The T allele of rs4142110 was correlated with higher levels of serum magnesium, phosphorus, and lower AKP level. The G alleles of rs4293393 was associated with higher serum CO2 level. The risk alleles of these SNPs were proved to be associated with the electrolytes metabolism that may result in the formation of urolithiasis.

Extramammary Paget’s disease (EMPD) is a rare malignancy, and little was known about its prognostic factors and optimal treatment. In the current study, we aimed to discuss clinical and pathological features of scrotal EMPD and determine the prognostic factors for cancer-specific survival and local recurrence. A total of 206 patients with scrotal EMPD lesions surgically treated at our institute were studied. All clinical and pathological data were reviewed. Immunohistochemical staining of TP53 and Ki67 was examined as well. At the last follow-up, 175 patients (84.95%) were alive. Twelve patients (5.83%) had died of the disease due to distant metastases. Fifteen patients (7.28%) developed local recurrences of scrotal EMPD. Ki67 expression was significantly elevated in patients with wide horizontal invasion (P = 0.003). In univariate analysis, high invasion level, presence of nodule, presence of lymphovascular invasion, adnexa invasion, lymph node metastasis and high p53 expression were significant factors for poor cancer-specific survival. In multivariate analysis, high p53 expression was significantly correlated with poor cancer-specific survival. Wide horizontal invasion was independently correlated with local recurrence-free survival of scrotal EMPD. In conclusion, wide horizontal invasion is an independent risk factor for local recurrence-free survival in the patients with scrotal EMPD.

Tumor markers Ki67, TP53, and TP63 are common labels in the diagnosis of bladder cancer (BCa) around the world. The combination of those biomarkers may have advantages in predicting BCa prognosis and non-muscle-invasive bladder cancer (NMIBC) postoperative recurrence. We investigated the immunohistochemical profiles of 313 bladder cancer samples classified under the WHO/ISUP (2004) grading scale and the UICC-TNM (2002) classification. Then we investigated their predictive value in the tumor recurrence of 270 NMIBC patients after TURBT. Expression of Ki67 correlates with grade, stage, tumor size, and tumor numbers. Semiquantitative evaluation of TP53 correlates with grade and invasive conditions. The positive expression rate of TP63 correlated with tumor grade and stage. The combined effect of TP53 and Ki67 revealed a predictive value in NMIBC recurrence. However, the positive TP63 expression did not show any protective effect in NMIBC recurrence. The expression of TP53 and Ki67 could be used to predict the risk of NMIBC recurrence postoperatively.

Objectives To evaluate whether there is a relation between expression of vascular endothelial growth factor (VEGF) and any of the paraneoplastic syndromes (PNS) in clear cell renal cell carcinoma (ccRCC) patients. Materials and methods A total of 667 patients with ccRCC and at least one PNS were included. Thorough history taking, physical examinations, and laboratory tests were used to diagnose PNS. Immunohistochemistry was performed for VEGF evaluation. Results There were 10 different PNS identified in the population. Sixty patients had a single paraneoplastic presentation. In all patients, presence of cachexia ( n = 267, P n = 40, P = 0.0014), and hypercalcemia ( n = 48, P = 0.0006) was correlated to VEGF expression. Correlation was neither acquired in Stauffer's syndrome, pyrexia, elevated erythrocyte sedimentation rate (ESR), anemia, thrombocytosis, hypertension, neuromyopathy nor obtained within patients with single PNS. Conclusions Relations between PNS and VEGF expression in renal cell carcinoma (RCC) has not been studied yet. The results we gained hereby can help us further understand the mechanistic of PNS in RCC.

Bladder cancer (BCa) remained a major health problem. Med19 was related to tumor growth of BCa. Bone morphogenetic proteins (BMPs) were reported to be critical in bone metastasis of cancer. We therefore investigated the relations between Med19 and BMPs in BCa and their effect on bone metastasis of BCa. Bladder cancer cell lines were cultured and interfered with Med19 shRNA and control. Expressions of BMP-1, BMP-2, BMP-4, BMP-5, BMP-6, BMP-7, BMP-9, and BMP-15 were studied between 2 groups. Fifty-two BCa samples were included for immunohistochemical staining of Med19 and BMP-2. Expressions were scored and studied statistically. Invasiveness was studied with Transwell assay. Silencing or Med19 in BCa cells induced altered expressions of BMPs. Increased expressions of BMP-1, BMP-4, BMP-6, BMP-7, and BMP-15 and decreased expressions of BMP-2, BMP-5, and BMP-9 were noticed, but only BMP-2 reached statistical significance. Expressions of Med19 and BMP-2 were significantly higher in cases with bone metastasis and were positively correlated in cases with bone metastasis and muscle invasion. Med19 is a critical factor involved in the invasiveness and promotion of bone metastasis of BCa, possibly via BMP-2.

Hypertension, hyperglycemia, and overweight are considered associated with the development and prognosis of prostate cancer (PCa). This study is aimed at investigating the association between pre-existing hypertension, hyperglycemia, and overweight and the overall survival (OS) of PCa patients receiving androgen deprivation therapy (ADT). We studied the clinical data of 323 patients of PCa receiving ADT in our hospital from January 2003 to August 2012 aged 50–91. The association between OS and hypertension, hyperglycemia, or overweight, both separately and together, was analyzed via Kaplan–Meier method. The distributions of clinicopathological features among groups were evaluated using Fisher’s exact or chi-square test. 23 men (7.12 %) were lost to follow-up during this study. During a median follow-up for 43 months (range 3–119 months), 122 deaths (40.67 %) were confirmed. The five-year OS rate of men with both hypertension and overweight (28.57 %) was significantly lower than that of control group (48.33 %, P = 0.024). It was also moderately lower than that of men just with hypertension (50.00 %, P = 0.095) or overweight (55.56 %, P = 0.088). Men with both hyperglycemia and overweight had significantly shorter survival time than control group (P = 0.037). The distributions of clinical information were similar among all the groups except that overweight patients had a lower proportion of PSA level over 20 ng/mL (65.38 %) than control group (84.95 %, P = 0.026). Pre-existing hypertension, hyperglycemia, and overweight were associated with poor prognosis of PCa patients. Men with both hypertension and overweight, or with both hyperglycemia and overweight had significantly shorter survival time.

Resumen Antecedentes y objetivos El cancer de prostata (CaP) es el cancer mas comun entre los hombres en la mayoria de las poblaciones occidentales. El gen de polimorfismos de la mieloperoxidasa (MPO) se ha correlacionado con la expresion anormal de la MPO y el aumento del riesgo de varios tipos de cancer. Nuestro estudio ha tenido como objetivo evaluar la asociacion entre los polimorfismos geneticos y el riesgo de cancer de prostata. Metodos La genotipificacion se realizo mediante el sistema de genotipificacion (MassARRAY IPLEX; Sequenom, Inc., San Diego, CA, EE. UU.) en 1.108 pacientes con CaP y 1.525 controles sin cancer en una poblacion china Han. Resultados Aunque un PNS (rs8082134, p Conclusion Nuestros datos mostraron una asociacion limitada entre los PNS de la MPO y la susceptibilidad al CaP en la poblacion china Han. La posible asociacion de rs8082134 de MPO con el riesgo de CaP necesita mas aclaraciones.

Background: Prior studies examining the relation between diabetes mellitus (DM) and prostate cancer risk have reported controversial findings. We examined this association by conducting a detailed meta-analysis of the peer-reviewed literature. Methods: A comprehensive search for articles of MEDLINE and EMBASE databases and bibliographies of retrieved articles published up to November, 2012 was performed. Methodological quality assessment of the trials was based on the Newcastle-Ottawa Scaleq and the meta-analysis was performed using STATA 12.0. Dose-response regression was conducted with SPSS 19.0. Results: We included 29 studies in the meta-analysis (13 case-control studies, 16 cohort studies), and found an inverse association between DM and prostate cancer (relative risk (RR) 0.84, 95% confidence interval (CI), 0.78-0.91). An inverse association was also observed in non-Asian populations (RR 0.81, 95% CI 0.76-0.87) and population-based studies (RR 0.80, 95% CI 0.77-0.91). No statistical significance was found of the association between prostate cancer risk and the duration of DM (p=0.338), and risk seemed not related with the age of DM diagnosis. Conclusions: This study suggested an inverse relationship between DM and prostate cancer, but without links to duration of disease or age of diagnosis.

Our previous study found that the activity of PCa-MSCs, which could stimulate the cell proliferation of RM-1, was significantly different compared to BMMSCs. Our results indicated that it could be mediated in part by growth factors/chemokines, which were involved in the different activity between two kinds of MSCs (PCa-MSCs and BMMSCs). Normal MSCs (BMMSCs) were isolated from the femur, tibia of the normal mice; prostate tumor MSCs (PCa-MSCs) were obtained from the mice implanted with prostate tumor. Analysis of the expression of SDF-1, CXCR4, VEGF, bFGF and vWF of two kinds of MSCs were examined by ELISA, Realtime-PCR and Western blotting. The expressions of SDF-1 and CXCR4 in PCa-MSCs were higher compared to BMMSCs. Expressions of bFGF and vWF were higher in PCa-MSCs yet the difference did not reach statistical significance. The expression of VEGF was significantly higher in PCa-MSCs. Our data showed that activity of PCa-MSCs was significantly improved compared with BMMSCs, which seemed to have an intrin- sic, cell-specific capacity localized to PCa. It could be induced by some factors or chemokines such as SDF-1, CXCR4, and VEGF. The possible role of PCa-MSCs in the process of PCa development needed further clarification.

// Guanxiong Ding 1, * , Jianqing Wang 1, * , Chenchen Feng 1 , Haowen Jiang 1 , Jianfeng Xu 1, 2 , Qiang Ding 1 1 Department of Urology, Huashan Hospital, Fudan University, Shanghai, China 2 Department of Urology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA * These authors have contributed equally to this work Correspondence to: Jianfeng Xu, email: drwang_shan@126.com Qiang Ding, email: dingqiang888@126.com Keywords: castration-resistant prostate cancer, lipocalin 2, androgen receptor, cell proliferation, transcriptional activity Received: April 25, 2016 Accepted: August 13, 2016 Published: September 01, 2016 ABSTRACT Background: Castration-resistant prostate cancer (CRPC) is the lethal phenotype of prostate cancer. Lipocalin 2 (LCN2) is aberrantly expressed in many cancers including primary prostate cancer (PCa), but its role in CRPC has not been reported. Results: LCN2 expression was upregulated in human primary PCa and CRPC tissues. Overexpression of LCN2 promoted C4-2B and 22RV1 cell proliferation while knockdown of LCN2 markedly inhibited C4-2B and 22RV1 cell growth. LCN2 overexpression led to increased AR downstream gene SLC45A3 without upregulating AR expression. In the xenograft model, overexpression of LCN2 significantly promoted tumor growth. Methods: LCN2 expression was detected in primary PCa and CRPC tissues and cell lines C4-2B and 22RV1 using immunohistochemistry and western blotting, respectively. Serum LCN2 level was detected vi ELISA. Lentiviruses-mediated over-expression of LCN2 and LCN2 knockdown were performed in CRPC cell lines. Expressions of androgen receptor (AR) downstream genes was examined in cell lines, in CRPC tissues, and in animal models. Conclusion: LCN2 could facilitate cell proliferation of CRPC via AR transcriptional activity. LCN2 could be a novel target in CRPC.

Prostate cancer (PCa) is the most common type of cancer worldwide. Mesenchymal stem cells (MSCs) can also be utilized as ‘tumor stromal cells’, which are associated with invasive and metastatic malignant tumor cells. Our study aimed to investigate MSCs in prostate tumors and normal MSCs and evaluate their differential characteristics. Normal MSCs (BMMSCs) were isolated from the femur and tibia of normal mice; prostate tumor MSCs (PCa-MSCs) were obtained from prostate tumors implanted in mice. These two types of MSCs were induced to differentiate into adipocytes, bone cells and chondrocytes. Growth curves were used to analyze the growth ability of PCa-MSCs and BMMSCs. Tritium-labeled thymidine (3H-TdR) was used to evaluate cell proliferation of RM-1 stimulated by MSCs. The time taken for PCa-MSCs to reach 90% confluence was markedly shorter than that of BMMSCs (8–10 vs. 12–14 days). The differentiation ability of PCa-MSCs was similar to that described in previous reports. The growth ability of PCa-MSCs was significantly higher than that of BMMSCs. The proliferative activity of PCa-MSCs was also higher than that of BMMSCs. Our data showed that PCa-MSCs exhibit identical characteristics when compared with those of MSCs. Additionally, their proliferative activity and growth ability were significantly higher when compared with these values in BMMSCs, which appear to have an intrinsic, cell-specific capacity to localize to PCa. The possible role of PCa-MSCs in the process of PCa development requires further clarification.

Objective: To investigate any association between renal cell carcinoma (RCC) and paraneoplastic syndromes (PNS). Subjects and Methods: The retrospective analysis included 1,028 patients of Chinese Han nationality with resectable RCC and PNS. The PNS included elevated erythrocyte sedimentation rate (ESR), hypertension, cachexia, anemia, pyrexia, abnormal liver function, hypercalcemia, polycythemia, varicocele and neuromyopathy. Staging was categorized as local (T1–2N0M0) and locally advanced (T3–4NxM0). Results: Among patients with at least one PNS, elevated ESR (p = 0.008), cachexia (p = 0.000), varicocele (p = 0.000) and pyrexia (p = 0.021) were related to advanced stage of RCC. Among patients with only one PNS, hypertension (p = 0.012) and hypercalcemia (p = 0.000) were related to advanced stage. The remaining PNS were not associated with tumor stage. Conclusion: Pyrexia, elevated ESR, cachexia and varicocele were related to advanced RCC. Hypertension and hypercalcemia occurring as single PNS, although also correlated with advanced stage, require further investigation.

Radical cystectomy (RC) is the gold standard treatment for patients with high-risk non-muscle-invasive bladder cancer and muscle-invasive bladder cancer (MIBC) . However, despite aggressive treatment, mortality rates of patients are still high. Therefore, it is crucial to indentify some practical prognostic factors for cancer-specific survival in those patients to guide our therapeutic strategies. We included 103 patients treated with RC for urothelial bladder cancer (UBC) between July 2007 and June 2014 in our institution and analyzed their clinicopathological parameters. The mean follow-up was 22 months (range 2–89 months). Advanced tumor T stage, N stage, ABO blood type, a history of DM and positive p63 expression were independent factors for worse survival in all patients who underwent RC. Moreover, in female gender, high Ki67 expression was significant risk factor for cancer-specific survival (CSS) in MIBC patients. Our study demonstrated that immunohistochemical expressions of Ki67 and p63 are potential prognostic factors for UBC patients who underwent RC.

We aimed to exploit novel compounds with high selectivity to clear cell renal cell carcinoma (ccRCC) with common mutations. Using the GDSC databases, we searched for compounds with high selectivity for ccRCC with VHL and/or SETD2 mutations. Clinical impact and gene interactions were analysed using TCGA database. In vitro and in vivo studies were performed to validate the inhibitory effects of the compound. We identified the selective PI3Kβ inhibitor TGX221 as a selective inhibitor for ccRCC with both VHL and SETD2 mutations. TGX221 also targeted cancer cells with CDKN2A and PTEN mutations. Changes in PTEN and CDKN2A gene sets were associated with worsened prognosis of ccRCC. TGX221 substantially and selectively inhibited the down stream products of VHL, SETD2 and PTEN in ccRCC cells with VHL and SETD2 mutations. TGX221 also exhibited significant selectivity in inhibiting cell motility and tumourigenesis of ccRCC cells with VHL and SETD2 mutations. TGX221 is a novel inhibitor with high selectivity for ccRCC with VHL and SETD2 mutations. It also targeted PTEN and CDKN2A mutations. How those genes were associated with PI3Kβ warranted further investigations.

Metastasis is the primary cause of prostate cancer (PCa) lethality and poses a huge clinical obstacle. Lipocalin 2 (LCN2), a member of the lipocalin family, is aberrantly expressed in some human cancers and has been implicated in the progression of some tumors. However, the role of LCN2 in the metastatic capacity of prostate cancer (PCa) is poorly understood.LCN2 expression was examined by RT-qPCR and/or immunoblotting in human prostate tissue specimens and prostate cancer cell lines LNCaP, C4-2, 22RV1, PC3, DU-145, and PC3MM2. LCN2 protein level in human serum samples was determined by ELISA. Lentiviruses-mediated over-expression of LCN2 and knockdown of LCN2 was conducted to evaluate the role of LCN2 in cell migratory and invasive capacities of prostate cancer cells. Cell migration and invasion was examined by transwell chamber assay. Knockdown of SLUG by lentivirus was performed to investigate its role in LCN2-promoted cell migration and invasion in vitro (22RV1 cell line) and metastasis in vivo (tail vein metastasis assay in nude mice). Role of ERK signaling in LCN2-mediated up-regulation of SLUG was assayed by using ERK inhibitor U0126.We confirmed that LCN2 levels were correlated positively with invasive prostate cancer in human tissue and serum samples, and were also consistently associated with the invasive capacity of prostate cancer cell lines. The over-expression of LCN2 in 22RV1 cells (not highly invasive) promoted the epithelial-mesenchymal transition (EMT), increasing cell motility and invasiveness, while the knockdown of LCN2 in PC3 cells (highly invasive) inhibited EMT, decreasing cell motility and invasiveness. Among the multiple EMT transcription factors, LCN2 specifically induces the expression of SLUG, which was shown here to be required for the LCN2-induced increase in the invasive capacity of prostate cancer cells both in vitro and in vivo. Mechanistically, LCN2 promoted SLUG expression via activating ERK signaling pathway.LCN2 plays an important role in promoting cell migration and invasion of prostate cancer by inducing EMT through the ERK/SLUG axis. Therefore, targeted inhibition of LCN2 may represent a therapeutic strategy to prevent the metastasis of prostate cancer.

Upper tract urothelial carcinoma (UTUC) is rare but aggressive with poor prognosis. We aimed to find effective predictive markers for recurrence and prognosis in UTUC patients. In this retrospective study, we included 88 UTUC patients treated with radical neprhoureterectomy (RNU) and analyzed their clinicopathological parameters. For study of incidence of metachronous bladder tumor, models were adjusted with inclusion of prophylactic intravesical instillation chemotherapy. The mean follow-up was 28.59 months (2 to 82 mo). Lack of gross hematuria (RR 0.060, 95%CI 0.008–0.468), tumor located at ureter (RR 0.037, 95%CI 0.004–0.378), advanced stage and higher p53 expression were independent factors for worse survival. Recurrence of bladder cancer occurred 20% of patients at median follow-up of 37.65 months (5 to 82 mo). Higher tumor grade (RR 5.998, 95%CI 1.359–26.479) and presence of ipsilateral non-functioning kidney at diagnosis (RR 5.982, 95%CI 1.338–26.750) were predictors for recurrence. The present study identified several parameters with predictive value in the prognosis and intravesicle recurrence in UTUCand shed light on the better monitoring and management of the disease.

Tumor markers TP53 and Ki67 are currently common labels used in the diagnosis of bladder cancer throughout the world. In light of the co-existence of both WHO1973 and 2004 classifications for bladder cancer, it is necessary to establish different quantification standards for both labels to better cater for the grading and staging.We investigated the immunohistochemical profiles of 280 bladder cancer samples classified under WHO 2004 standards. TP53 was scored semi-quantitatively whilst Ki67 was scored by label index.We found that expression of TP53 was not correlated to either grade or stage, a finding that doesn't agree with most of the literature. Expression of Ki67 was correlated with grade and stage. Expressions of TP53 and Ki67 were correlated with each other. Interestingly, Ki67 expression was higher in females.The expression of TP53 could be modified to better suit the WHO 2004 classification.

To investigate the correlation between parathyroid hormone-related protein (PTHrP), erythropoietin (EPO), and vascular endothelial growth factor (VEGF) expression in clear cell renal cell carcinoma (ccRCC). Immunohistochemical studies on PTHrP, EPO and VEGF were performed in 249 patients with ccRCC. Serum calcium level and haematocrit were analyzed. The expression of the factors and clinicopathological parameters were studied statistically for possible correlations. The incidence for hypercalcaemia and polycythaemia were 15.3 % and 2.0 % respectively. Expression of PTHrP, EPO, and VEGF were respectively related to advanced stage (P

Though prostate cancer (PCa) has slow progression, the hormone refractory (HRCP) and metastatic entities are substantially lethal and lack effective treatments. Transcription factor Slug is critical in regulating metastases of various tumors including PCa. Here we studied targeted therapy against Slug using combination of 3 drugs targeting 3 pathways respectively converging via Slug and further regulating PCa metastasis. Using in vitro assays we confirmed that Slug up-regulation incurred inhibition of E-cadherin that was anti-metastatic, and inhibited Bim-regulated cell apoptosis in PCa. Upstream PTEN/Akt, mTOR, Erk, and AR/Hsp90 pathways were responsible for Slug up-regulation and each of these could be targeted by rapamycin, CI-1040, and 17-AAG respectively. In 4 PCa cell lines with different traits in terms of PTEN loss and androgen sensitivity we tested the efficacy of mono- and combined therapy with the drugs. We found that metastatic capacity of the cells was maximally inhibited only when all 3 drugs were combined, due to the crosstalk between the pathways. 17-AAG decreases Slug expression via blockade of HSP90-dependent AR stability. Combination of rapamycin and CI-1040 diminishes invasiveness more potently in PCa cells that are androgen insensitive and with PTEN loss. Slug inhibited Bim-mediated apoptosis that could be rescued by mTOR/Erk/HSP90 inhibitors. Using mouse models for circulating PCa DNA quantification, we found that combination of mTOR/Erk/HSP90 inhibitors reduced circulating PCa cells in vivo significantly more potently than combination of 2 or monotherapy. Conclusively, combination of mTOR/Erk/Hsp90 inhibits metastatic capacity of prostate cancer via Slug inhibition.

Zinc finger protein X-linked (ZFX) is a highly conservative mammalian gene with related functions in cell survival and proliferation. However, there are limited reports on regulation of ZFX as a therapeutic target in cancer treatment. In this study, the expression of ZFX in prostate cancer with matched normal adjacent tissues (n=45) and benign prostatic hyperplasia (BPH) tissues (n=16) were observed by immunohistochemical analysis. The effect of lentiviral siRNA (small interference RNA)-mediated dysfunction of ZFX on the proliferation of prostate cancer cells was studied. ZFX mRNA and protein expression levels in prostate cancer cells (PC-3 and DU145) were analyzed by western blotting and real-time polymerase chain reaction (RT-PCR). The effects of siRNA targeting ZFX on growth, cell cycle and apoptosis of PC-3 cells were evaluated by MTT assay and flow cytometry. We also investigated the effect of ZFX deletion on the activation of caspase-1, -3 and -9 by western blotting and colorimetric assay. Prostate cancer specimens appeared significantly higher (42.2% of cases being positive) than that observed in normal adjacent tissues (11.8% of cases being positive) and BPH tissues (12.5% of cases being positive). Repression of ZFX in the prostate cancer cells effectively suppressed the cellular proliferation and colony-formation ability, and led to G1 phase cell cycle arrest. Moreover, inhibition of ZFX-induced cell apoptosis by activating caspase-1, -3 and -9. In conclusion, ZFX represents the prominent role in the progression of prostate cancer and may be a promising therapy target for prostate cancer.

Oxidative stress was associated with prostate cancer (PCa). The expressions of prooxidant or antioxidant enzymes (myeloperoxidase [MPO], superoxide dismutase (SOD2), and catalase (CAT)) have been proved to be related to gene polymorphisms. Our study aimed to evaluate the association between genetic polymorphisms and the risk of PCa.Genotyping was carried out by genotyping system (MassARRAY iPLEX; Sequenom Inc, San Diego, CA) in 1388 patients with PCa and 1008 cancer-free controls in the Chinese population.One SNP of SOD2 (rs5746136; P.050, odds ratios (OR), 0.8806) was significant. Another SNP was shown to have limited association with the risk of PCa (rs554518; P = .09443) in all SNPs of CAT. In other SNPs, no significant difference was shown between genotype distributions in the patients with PCa and the control group.Our data showed that rs5746136 of SOD2 was associated with susceptibility to PCa in the Chinese population of Han nationality. The possible association between rs8082134 of CAT and PCa risk needs further verification.