Novel potential urinary biomarkers for effective diagnosis and prognostic evaluation of high-grade bladder cancer.

Background: High-grade bladder cancer (HGBC) has a higher malignant potential, recurrence and progression rate compared to low-grade phenotype. Its early symptoms are often vague, making non-invasive diagnosis using urinary biomarkers a promising approach. Methods: The gene expression data from urine samples of patients with HGBC was extracted from the GSE68020 dataset. The clinical information and gene expression data in tumor tissues of HGBC patients were obtained from The Cancer Genome Atlas (TCGA) database. Multivariate Cox analysis was used to predict the optimal risk model. The protein-protein interaction (PPI) analysis was performed via the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized using Cytoscape. Overall survival (OS) was evaluated in the Gene Expression Profiling Interactive Analysis (GEPIA) online platform. Competing endogenous RNA (ceRNA) network was also visualized using Cytoscape. The expression levels of specific genes were assessed through quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Moreover, co-expressed genes and potential biological functions related to specific genes were explored based on the Cancer Cell Line Encyclopedia (CCLE) database. Results: A total of 560 differentially expressed genes (DEGs) were identified when comparing the urine sediment samples from HGBC patients with the benign ones. Using these urinary DEGs and the clinical information of HGBC patients, we developed an optimal risk model consisting of eight genes to predict the patient outcome. By integrating the node degree values in the PPI network with the expression changes in both urine and tissue samples, eighteen hub genes were selected out. Among them, DKC1 and SNRPG had the most prominent comprehensive values, and EFTUD2, LOR and EBNA1BP2 were relevant to a worse OS in bladder cancer patients. The ceRNA network of hub genes indicated that DKC1 may be directly regulated by miR-150 in HGBC. The upregulation of both SNRPG and DKC1 were detected in HGBC cells, which were also observed in various tumor tissues and malignant cell lines, displaying high correlations with other hub genes. Conclusions: Our study may provide theoretical basis for the development of effective non-invasive detection and treatment strategies, and further research is necessary to explore the clinical applications of these findings.

High S100A7 expression is associated with early muscle invasion and poor survival in bladder carcinoma.

Muscle-invasive bladder carcinoma (MIBC) accounts for 25% of newly diagnosed bladder carcinomas (BCs) and presents a high risk of progression and metastasis. This study aimed to identify reliable biomarkers associated with muscle invasion and prognosis to identify potential therapeutic targets for MIBC. Four gene datasets were downloaded from the Gene Expression Omnibus, and the integrated differentially expressed genes (DEGs) were then subjected to gene ontology (GO) terms and pathway enrichment analyses. Correlation analysis between the expression of the top-ranking DEGs and pathological T stages was performed to identify the genes associated with early muscle invasion. The corresponding prognostic values were evaluated, and co-expressed genes mined in the cBioPortal database were loaded into ClueGo in Cytoscape for pathway enrichment analysis. Using data mining from the STRING and TCGA databases, protein-protein interaction and competitive endogenous RNA networks were constructed. In total, 645 integrated DEGs were identified and these were mainly enriched in 26 pathways, including cell cycle, bladder cancer, DNA replication, and PPAR signaling pathway. S100A7 expression was significantly increased from the T2 stage and showed significantly worse overall survival and disease-specific survival in patients with BC. In total, 144 genes co-expressed with S100A7 in BC were significantly enriched in the IL-17 pathway. S100A7 was predicted to directly interact with LYZ, which potentially shows competitive binding with hsa-mir-140 to affect the expression of six lncRNAs in MIBC. In conclusion, high S100A7 expression was predicted to be associated with early muscle invasion and poor survival in patients with BC.

Role of NRP1 in Bladder Cancer Pathogenesis and Progression.

Bladder urothelial carcinoma (BC) is a fatal invasive malignancy and the most common malignancy of the urinary system. In the current study, we investigated the function and mechanisms of Neuropilin-1 (NRP1), the co-receptor for vascular endothelial growth factor, in BC pathogenesis and progression. The expression of NRP1 was evaluated using data extracted from GEO and HPA databases and examined in BC cell lines. The effect on proliferation, apoptosis, angiogenesis, migration, and invasion of BC cells were validated after NRP1 knockdown. After identifying differentially expressed genes (DEGs) induced by NRP1 silencing, GO/KEGG and IPA® bioinformatics analyses were performed and specific predicted pathways and targets were confirmed in vitro. Additionally, the co-expressed genes and ceRNA network were predicted using data downloaded from CCLE and TCGA databases, respectively. High expression of NRP1 was observed in BC tissues and cells. NRP1 knockdown promoted apoptosis and suppressed proliferation, angiogenesis, migration, and invasion of BC cells. Additionally, after NRP1 silencing the activity of MAPK signaling and molecular mechanisms of cancer pathways were predicted by KEGG and IPA® pathway analysis and validated using western blot in BC cells. NRP1 knockdown also affected various biological functions, including antiviral response, immune response, cell cycle, proliferation and migration of cells, and neovascularisation. Furthermore, the main upstream molecule of the DEGs induced by NRP1 knockdown may be NUPR1, and NRP1 was also the downstream target of NUPR1 and essential for regulation of FOXP3 expression to activate neovascularisation. DCBLD2 was positively regulated by NRP1, and PPAR signaling was significantly associated with low NRP1 expression. We also found that NRP1 was a predicted target of miR-204, miR-143, miR-145, and miR-195 in BC development. Our data provide evidence for the biological function and molecular aetiology of NRP1 in BC and for the first time demonstrated an association between NRP1 and NUPR1, FOXP3, and DCBLD2. Specifically, downregulation of NRP1 contributes to BC progression, which is associated with activation of MAPK signaling and molecular mechanisms involved in cancer pathways. Therefore, NRP1 may serve as a target for new therapeutic strategies to treat BC and other cancers.

A case of flank pain caused by ureteral intussusception accompanied with ureteral polyp.

BACKGROUND: Ureteral intussusception, a rarely reported unique condition, occurs primarily as a complication of ureteric tumours. CASE PRESENTATION: We present a case of ureteral intussusception accompanied with a large ureteral polyp periodically protruding into the bladder cavity occurring in a 56-year-old man who experienced vague flank pain and intermittent haematuria. The patient was successfully treated by ureteroscopic cauterization combined with partial ureterectomy with reanastomosis. CONCLUSIONS: This is the first report that describes polyp-related ureteral intussusception using comprehensive and representative ureteroscopic images and video. Our findings suggest that ureteroscopy is vital for diagnosis. Extensive biopsies through ureteroscopy are less invasive, and make it easier to exclude the presence of ureteral malignancies. Ureteroscopic resection of the whole polyp with its stalk and intussusceptum using Holmium: YAG laser did not seem viable in this case. However, cauterization of partial polyp tissues followed by open surgery for segmental resection of the ureter with reanastomosis is helpful in controlling such patient well-being.

[Experimental study on relationship between TCM syndrome type and gastric mucosa cell proliferation in rat model of chronic atrophic gastritis].

OBJECTIVE: To explore the relationship between TCM syndrome type and gastric mucosa cell proliferation related controlling gene protein in chronic atrophic gastritis (CAG). METHODS: Expressions of cell proliferation related controlling gene protein, including proliferative cell nuclear antigen (PCNA), epidermal growth factor receptor (EGFR) and c-myc, from gastric mucosa of CAG model rats with different syndrome types were measured by immunohistochemistry and the changes of them before and after TCM intervention were also analyzed by image analysis. RESULTS: Protein expressions of PCNA, EGFR and c-myc in gastric mucosa of CAG model rats with different syndrome types (Pi-deficiency type, Gan-stagnation type and dampness-heat type) were different to some extent, and all of them reduced significantly after TCM intervention in the model rats of all syndrome types. CONCLUSION: Expressions of cell proliferation related controlling gene protein in gastric mucosa of CAG model rats of different syndrome types were different to some extent, which provides a certain experimental evidence for revealing the essence of TCM syndrome type of CAG and judging the prognosis of various types.