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.

Image-guided radiofrequency ablation for adrenal metastatic tumors: a systematic review and meta-analysis.

PURPOSE: To evaluate the safety and clinical efficacy of image-guided radiofrequency ablation (RFA) in patients exhibiting adrenal metastatic tumors (AMTs). METHODS: The PubMed, Web of Science, and Wanfang databases were searched for relevant studies published as of November 2022, and study results were pooled for subsequent analysis. The endpoints of this meta-analysis included primary and secondary technical success, local hemorrhage, pneumothorax, hypertensive crisis, local recurrence, and 1- and 3-year overall survival (OS) rates. RESULTS: This analysis incorporated 11 studies enrolling 351 patients that underwent RFA treatment for 373 AMTs. The pooled primary and secondary technical success, local hemorrhage, pneumothorax, hypertensive crisis, local recurrence, and 1- and 3-year OS rates in these patients were 84%, 91%, 4%, 6%, 7%, 19%, 82%, and 46%, respectively. The 1-year OS (I2 = 75.2%, p = 0.003) and 3-year OS (I2 = 81.4%, p = 0.001) endpoints were subject to significant heterogeneity. Subgroup analyses suggested that primary technical success rates were < 80% in patients with tumors exhibiting a mean diameter ≥ 4 cm. Guidance type and tumor size had no impact on a hypertensive crisis or local recurrence rates. CONCLUSIONS: These data indicate that image-guided RFA represents a safe and effective means of treating AMTs.

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.

Identification of C3 and FN1 as potential biomarkers associated with progression and prognosis for clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most lethal urological malignancies, but the pathogenesis and prognosis of ccRCC remain obscure, which need to be better understand. METHODS: Differentially expressed genes were identified and function enrichment analyses were performed using three publicly available ccRCC gene expression profiles downloaded from the Gene Expression Omnibus database. The protein-protein interaction and the competing endogenous RNA (ceRNA) networks were visualized by Cytoscape. Multivariate Cox analysis was used to predict an optimal risk mode, and the survival analysis was performed with the Kaplan-Meier curve and log-rank test. Protein expression data were downloaded from Clinical Proteomic Tumor Analysis Consortium database and Human Protein Atlas database, and the clinical information as well as the corresponding lncRNA and miRNA expression data were obtained via The Cancer Genome Atlas database. The co-expressed genes and potential function of candidate genes were explored using data exacted from the Cancer Cell Line Encyclopedia database. RESULTS: Of the 1044 differentially expressed genes shared across the three datasets, 461 were upregulated, and 583 were downregulated, which significantly enriched in multiple immunoregulatory-related biological process and tumor-associated pathways, such as HIF-1, PI3K-AKT, P53 and Rap1 signaling pathways. In the most significant module, 36 hub genes were identified and were predominantly enriched in inflammatory response and immune and biotic stimulus pathways. Survival analysis and validation of the hub genes at the mRNA and protein expression levels suggested that these genes, particularly complement component 3 (C3) and fibronectin 1 (FN1), were primarily responsible for ccRCC tumorigenesis and progression. Increased expression of C3 or FN1 was also associated with advanced clinical stage, high pathological grade, and poor survival in patients with ccRCC. Univariate and multivariate Cox regression analysis qualified the expression levels of the two genes as candidate biomarkers for predicting poor survival. FN1 was potentially regulated by miR-429, miR-216b and miR-217, and constructed a bridge to C3 and C3AR1 in the ceRNA network, indicating a critical position of FN1. CONCLUSIONS: The biomarkers C3 and FN1 could provide theoretical support for the development of a novel prognostic tool to advance ccRCC diagnosis and targeted therapy.

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 network pharmacology perspective for deciphering potential mechanisms of action of Solanum nigrum L. in bladder cancer.

BACKGROUND: Solanum nigrum L. decoction has been used as a folklore medicine in China to prevent the postoperative recurrence of bladder cancer (BC). However, there are no previous pharmacological studies on the protective mechanisms of this activity of the plant. Thus, this study aimed to perform a systematic analysis and to predict the potential action mechanisms underlying S. nigrum activity in BC based on network pharmacology. METHODS: Based on network pharmacology, the active ingredients of S. nigrum and the corresponding targets were identified using the Traditional Chinese Medicines for Systems Pharmacology Database and Analysis Platform database, and BC-related genes were screened using GeneCards and the Online Mendelian Inheritance in Man database. In addition, ingredient-target (I-T) and protein-protein interaction (PPI) networks were constructed using STRING and Cytoscape, Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted, and then the pathways directly related to BC were integrated manually to reveal the pharmacological mechanism underlying S. nigrum-medicated therapeutic effects in BC. RESULTS: Seven active herbal ingredients from 39 components of S. nigrum were identified, which shared 77 common target genes related to BC. I-T network analysis revealed that quercetin was associated with all targets and that NCOA2 was targeted by four ingredients. Besides, interleukin 6 had the highest degree value in the PPI network, indicating a hub role. A subsequent gene enrichment analysis yielded 86 significant GO terms and 89 significant pathways, implying that S. nigrum had therapeutic benefits in BC through multi-pathway effects, including the HIF-1, TNF, P53, MAPK, PI3K/Akt, apoptosis and bladder cancer pathway. CONCLUSIONS: S. nigrum may mediate pharmacological effects in BC through multi-target and various signaling pathways. Further validation is required experimentally. Network pharmacology approach provides a predicative novel strategy to reveal the holistic mechanism of action of herbs.

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.