Expression patterns and a prognostic model of m6A-associated regulators in prostate adenocarcinoma.

Aim: To study the expression patterns and prognostic value of the m6A-associated regulators in prostate adenocarcinoma (PRAD). Materials & methods: The mRNA expression and clinical data were downloaded from 'The Cancer Genome Atlas database'. The m6A-associated variants were downloaded from m6AVar database, and combined with 14 common m6A regulators for subsequent analysis. One-way analysis of variance, univariate Cox regression analysis and least absolute shrinkage and selection operator algorithm were successively applied to obtain the ultimate regulators and prognostic model. Finally, consensus clustering, protein-protein interaction (PPI) and enrichment analysis were performed. Result: Nine regulators were obtained. PRAD patients could be classified into two risk groups and subclasses with significant survival differences by the prognostic model and consensus clustering, respectively. Conclusion: All these nine regulators were related to prognosis in PRAD, and could be used as clinical biomarkers.

Downregulation of ST3GAL5 is associated with muscle invasion, high grade and a poor prognosis in patients with bladder cancer.

In patients with bladder cancer (BC), the association between ST3 ß-galactoside α-2,3-sialyltransferase 5 (ST3GAL5) expression and clinical outcomes, particularly regarding muscle-invasive disease, high tumor grade and prognosis, remain unknown. In the present study, the expression of ST3GAL5 and its association with clinical outcomes in patients with BC was analyzed using various public bioinformatics databases. The difference in ST3GAL5 expression between BC and healthy bladder tissues was also evaluated using data from the Oncomine database, The Cancer Genome Atlas and Gene Expression Omnibus database. The differences in ST3GAL5 expression between muscle invasive BC (MIBC) and non-muscle invasive BC (NMIBC), and high- and low-grade BC were also analyzed. Furthermore, genes that were positively co-expressed with ST3GAL5 in patients with BC were identified from the intersection between the Oncomine, Gene Expression Profiling Interactive Analysis 2 and UALCAN databases. Enrichment analysis by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome pathway enrichment analyses and a gene-concept network was performed using R package. Gene set enrichment analysis was also performed to assess the signaling pathways influenced by the high and low expression of ST3GAL5 in BC. The results indicated that ST3GAL5 expression was significantly lower in BC tissues compared with normal bladder tissues (P<0.05). Furthermore, ST3GAL5 expression in MIBC and high-grade BC was significantly lower compared with NMIBC and low-grade BC (P<0.05), respectively. The results from Kaplan-Meier survival analysis result demonstrated that ST3GAL5 downregulation was associated with poor survival in patients with BC (P<0.05). Taken together, these findings suggested that ST3GAL5 may be considered as an anti-oncogene in BC, could represent a potential predictive and prognostic biomarker for BC and may be a molecular target for tumor therapy.

Upregulation of RAC3 in bladder cancer predicts adverse clinical outcome and increased tumor immune response.

The relationship between RAC3 expression and clinical outcome in bladder cancer (BLCA) was uncertain. In this study, the expression level of RAC3 in BLCA and its clinical outcome were analyzed through various independent public databases. The mRNA expression level of RAC3 in BLCA and normal bladder was evaluated from the Gene Expression Omnibus (GEO), Oncomine, and The Cancer Genome Atlas (TCGA) database. The protein expression of RAC3 in BLCA and normal bladder was investigated from immunohistochemical images through the Human Protein Atlas (HPA) database. Next, gene tumor immune analyses were performed. Furthermore, gene set enrichment analysis (GESA) by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG) for RAC3 and its co-expressed genes were performed. Then, GESA was also performed to validate the KEGG pathways by the different expression of RAC3 in BLCA. The results indicated that, compared with normal bladder, the mRNA and protein expression of RAC3 in BLCA were both significantly higher than those of normal bladder tissues (P<0.05). The tumor immune analyses indicated RAC3 was associated with microsatellite instability, tumor mutational burden, tumor immune microenvironment, and immune cell infiltration level evaluation (P<0.05). The survival analysis result demonstrated that upregulation of RAC3 was associated with adverse survival in BLCA (P<0.05). Taken together, these findings suggest that RAC3 may be associated with adverse clinical outcome and increased tumor immune response in BLCA, and may be a prognostic and immunotherapy marker for BLCA.

Low dose of interferon-α improves the clinical outcomes of docetaxel in patients with castration-resistant prostate cancer: A pilot study.

The aim of this study was to test whether a low dose of interferon-α-2b (IFN-α2b) enhances the clinical outcome of docetaxel (DXT) in patients with castration-resistant prostate cancer (CRPC). A prospective controlled trial of 40 CRPC patients receiving 5 mg of prednisone twice daily was conducted, where patients were randomly assigned to be administered 75 mg/m2 DXT plus 3 mIU/m2 IFN-α2b (group A, n=20) or 75 mg/m2 DXT alone (group B, n=20). The prostate-specific antigen (PSA) response, tumor response, progression-free survival (PFS) and overall survival (OS) were evaluated. There was no statistically significant difference in PSA response rate between groups A and B (65 vs. 47.4%, P=0.341). The tumor response rate in group A was significantly greater compared with that in group B (55 vs. 21.1%, P=0.048). The median PFS was longer in group A compared with that in group B (10 vs. 8 months, P=0.043). There was no statistically significant difference in median OS between the two groups (19 vs. 17 months, P=0.348), but one patient displayed a complete tumor response in group A. In groups A and B, transient grade 3 to 4 neutropenia was observed in nine and six patients, grade 3 to 4 anemia was observed in three and five patients, and grade 3 to 4 general fatigue was observed in four and one patient(s), respectively. The proportion of patients with grade 3 to 4 toxicity was not statistically different between the two groups. A low dosage of IFN-α2b may improve the antitumor activity of DXT with an acceptable toxicity profile in patients with CRPC.

Interstitial cells of Cajal mediate excitatory sympathetic neurotransmission in guinea pig prostate.

Morphological and functional studies have confirmed that interstitial cells of Cajal (ICCs) are involved in many enteric motor neurotransmission pathways. Recent investigations have demonstrated that human and guinea pig prostate glands possess a distinct cell type with morphological and immunological similarities to ICCs. These prostate ICCs have a close relationship with nerve bundles and smooth muscle cells. Prostate smooth muscle tone is largely induced by stimulation from the sympathetic nervous system, which releases excitatory norepinephrine (NE) to act on the α1-adrenoceptor. We have performed morphological and functional experiments to determine the role of ICCs in sympathetic neurotransmission in the guinea pig prostate based on the hypothesis that prostate ICCs act as mediators of sympathetic neurotransmission. Immunohistochemistry revealed many close points of contact between ICCs and sympathetic nerve bundles and smooth muscle cells. Double-labeled sections revealed that α1-adrenoceptor and the gap junction protein connexin 43 were expressed in prostate ICCs. Surprisingly, prostate ICCs co-expressed tyrosine hydroxylase and dopamine ß-hydroxylase, two markers of sympathetic neurons. Functionally, the application of NE evoked a large single inward current in isolated prostate ICCs in a dose-dependent manner. The inward current evoked by NE was mediated via the activation of α1-adrenoceptors, because it was abolished by the non-specific α-adrenoceptor antagonist, phentolamine and the specific α1-adrenoceptor antagonist, prazosin. Thus, ICCs in the guinea pig prostate are target cells for prostate sympathetic nerves and possess the morphological and functional characteristics required to mediate sympathetic signals.

[Inhibitory effect of dihydroartemisinin on the growth of human prostate cancer PC-3M cells and its mechanism].

OBJECTIVE: To study the effects of dihydroartemisinin on the apoptosis of and the vascular endothelial growth factor (VEGF) expression in prostate cancer cell line PC-3M in androgen-independent prostate cancer. METHODS: PC-3M cells were treated with different doses (0, 25, 50 and 100 micromol/L) of dihydroartemisinin for 48 hours, their growth activity analyzed by MTT colorimetric assay and flow cytometry, and changes in the activities of caspase-3 and -8 detected by colorimetric assay. The expression of VEGF mRNA was determined by semi-quantitative RT-PCR, and that of the VEGF protein by Western blotting. RESULTS: Compared with the 0 micromol/L control group, the 25, 50 and 100 micromol/L dihydroartemisinin groups showed significantly increased apoptosis of PC-3M cells ([2.92 +/- 0.45]% vs [8.85 +/- 0.74]%, [12.83 +/- 0.84]% and [18.65 +/- 1.24]%, P < 0.01), and dose-dependent increase in the activities of caspase-8 ([0.47 +/- 0.05 ] U/microg vs [1.22 +/- 0.15], [1.76 +/- 0.07] and [2.91 +/- 0.24] U/microg, P < 0.01) and caspase-3 ([0.44 +/- 0.07] U/microg vs [0.95 +/- 0.08], [1.48 +/- 0.14] and [2.92 +/- 0.45] U/microg, P < 0.01). The expressions of VEGF mRNA and protein were decreased in a concentration-dependent manner. CONCLUSION: Dihydroartemisinin can significantly suppress the growth of PC-3M cells, promote their apoptosis and reduce the expressions of VEGF mRNA and protein, which may serve to explain its inhibitory effect on tumor and angiogenesis.

[Primary non-Hodgkin's lymphoma of the testis and penis: clinical analysis of 5 cases].

OBJECTIVE: To improve the clinical diagnosis and treatment of primary non-Hodgkin's lymphoma of male genitalia. METHODS: We retrospectively reviewed the clinical data of 5 cases of primary non-Hodgkin's lymphoma of male genitalia, 4 in the testis and 1 in the penis, we also analyzed the relevant literature and clinical significance of the disease. RESULTS: All the 5 cases were treated by surgery and pathologically confirmed to be non-Hodgkin's lymphoma. Three of them received chemotherapy, and the other 2 (1 in the testis and 1 in the penis) underwent both chemotherapy and radiotherapy after the operation. Follow-up averaged 25 months, during which 1 of the patients died and the other 4 survived. CONCLUSION: Primary non-Hodgkin's lymphoma of male genitalia is an uncommon disease with atypical clinical presentations and poor prognosis, which occurs mostly in elderly males. Definite diagnosis of the disease mainly depends on histopathology and immunohistochemistry. Surgery with multiagent chemotherapy and radiotherapy is advisable for its treatment.

[Tumor infiltrating dendritic cells and Mucin1 gene expression in benign prostatic hyperplasia and prostate cancer].

OBJECTIVE: To study the expression of Mucin1 gene and tumor infiltrating dendritic cells(TIDC) in the tissues of benign prostatic hyperplasia (BPH) and prostate cancer. METHODS: Mucin1 and TIDC were detected in 20 specimens of BPH and 30 specimens of prostate cancer by immunohistochemistry SP method. RESULTS: MUC1 expressed in both prostate cancer and BPH. The staining patterns were significantly associated with tumor pathological grade (P < 0.001). The number of TIDC was negatively correlated with tumor pathological grade, the higher the grade, the smaller the number of TIDC (P < 0.001). CONCLUSIONS: The expression pattern of MUC1 and the number of TIDC could be considered as useful markers to evaluate the malignant degree and prognosis of prostate cancer. The decrease of TIDC plays an important role in tumor immune evasion and immune tolerance. Highly expressed MUC1 could lead to the failure of hormonal treatment for prostate cancer, and contribute much to tumor infiltration and metastasis.