Prognosis Of Bladder Cancer Patients Research Articles

NOTCH3 promotes malignant progression of bladder cancer by directly regulating SPP1 and activating PI3K/AKT pathway

The biological role and precise molecular mechanisms of Notch receptor 3 (NOTCH3) in the malignant progression of bladder cancer (BLCA) remain unclear. In this study, we found that NOTCH3 was significantly upregulated and associated with poor prognosis in BLCA patients. Functional experiments demonstrated that NOTCH3 knockdown inhibited BLCA cell proliferation, migration, invasion and significantly suppressed tumor growth and metastasis in vivo as well. Mechanically, chromatin immunoprecipitation and dual-luciferase reporter assays confirmed that NOTCH3 could promote the transcription of secreted phosphoprotein 1 (SPP1), a potential downstream target gene of NOTCH3, by binding to the CSL elements in the SPP1 promoter. Moreover, we also found that targeting NOTCH3 inhibited BLCA growth and metastasis by suppressing the SPP1-PI3K/AKT axis. Our study highlights the critical role of NOTCH3-SPP1-PI3K/AKT axis in the malignant progression of BLCA, suggesting that NOTCH3 may be a potential therapeutic target for BLCA.

A modified model of PANoptosisto identify prognosis and immunotherapy response in bladder cancer

BackgroundCell death, including apoptosis and necrosis, collectively known as widespread apoptosis. The present study aims to investigate the mechanism of action in widespread apoptosis-related modification patterns in bladder cancer. MethodsUsing a clinical genomics database, we obtained transcriptomic data and related clinical information of bladder cancer patients. By employing the least absolute shrinkage analysis, we were able to construct a risk model and single-cell sequencing analysis of differential genes in bladder cancer. ResultsFive differentially expressed genes (TMPRSS4, TPST1, FOXD1, ELOVL4, EMP1) associated with widespread apoptosis were identified as features for predicting the prognosis of bladder cancer patients. Survival curve analysis revealed significant differences in prognosis (P<0.05). Additionally, multivariate Cox regression analysis determined the independent risk factor for bladder cancer prognosis as the risk score (P<0.001), with high confidence in the scoring model validated internally (P<0.001). Single-cell sequencing reveals high expression of CDKN2A, ERBB2, and TMPRSS4 in B cells, while HRAS is significantly expressed in fibroblasts. ConclusionPANscore, as a potential prognostic and immunotherapeutic biomarker, will provide more precise and rational basis for personalized treatment strategies

Diagnostic Study Of Bladder Cancer Using Urine Methylation Biomarkers Of Iraqi Patients

Background: Bladder cancer (BC) is the 4th most frequently occurring malignancy and the 9th most common cause of death worldwide in men. The invasive and metastatic form of the cancer is the main cause of death or unfavorable prognosis for BC patients. The presence of a bladder tumor is often discovered after episodes of painless macroscopic hematuria. At initial diagnosis, the disease is non-muscle-invasive in approximately 75% of patients. In recent years, detecting aberrantly methylated DNA in urine has emerged as a promising and noninvasive approach to aid BC diagnosis. Objective: To detect bladder tumors in Iraqi patients. Methods: In this cross-sectional study, sixty cases were suspected of having bladder tumors according to the opinion of the physician and some signs and symptoms, the best sign was hematuria in urine (per diagnosis). An additional 30 healthy controls with similar age and sex were recruited as control groups, with an average age of 37_85 years. from Baghdad Medical City / Ghazi al–Hariri Teaching Hospital and AlKindi Specialized Hospital during the period from September / 2023 to April / 2024. Using molecular polymerase chain reaction (high-resolution melting-PCR). Results: Out of 60 bladder inflammations, the result of hypermethylation genes ZNF154, EOMES, and POU4F2, Sensitivity were (71.7, 85, and 75) %, and Specificity (60, 33.3, and 50) % respectively with high significant differences (p &lt; 0.01). In addition. Conclusions: Detecting DNA hypermethylation is considered a good diagnosis method for bladder tumors.

Intratumoral microbiota as a novel prognostic indicator in bladder cancer

Microbes are important components of the tumor microenvironment and have a close relationship with tumors. However, there is still a lack of research on the intratumoral microbiota in bladder cancer and its impact on the tumor immune microenvironment. In this study, we used fluorescence in situ hybridization (FISH) and observed a substantial presence of microbiota in bladder cancer tissues, with greater abundance compared to that in normal bladder tissues. Based on the BIC database, we found that the microbiome of bladder cancer is highly diverse and its structure is significantly different from that of other tumors. To investigate the relationships among the intratumoral microbiota, tumor immunity, and prognosis in bladder cancer patients, we analyzed bladder cancer-specific differentially expressed immune- and antimicrobial-related genes from the ImmPort, TISIDB, and TCGA databases. We identified 11 hub genes and constructed a prognostic risk model. Further analysis revealed differences at the family and genus levels between distinct groups. Using LEfSe analysis, we identified six hub biomarkers and developed a novel microbial-based scoring system. The scoring system allows subgrouping of bladder cancer patients, with significant differences in prognosis, immune cell infiltration, tumor mutation burden, and immune checkpoints among different groups. Further FISH and immunofluorescence co-staining experiments initially verified that the specific distribution of microorganisms and M2 macrophages in bladder cancer may be closely related to the poor prognosis of patients. In conclusion, this study revealed the characteristics of the intratumoral microbiota in bladder cancer and identified potential prognostic targets for clinical application.

Liquid-liquid phase separation-related genes associated with prognosis, tumor microenvironment characteristics, and tumor cell features in bladder cancer.

This study aimed to explore the Liquid-liquid phase separation (LLPS)-related genes associated with the prognosis of bladder cancer (BCa) and assess the potential application of LLPS-related prognostic signature for predicting prognosis in BCa patients. Clinical information and transcriptome data of BCa patients were extracted from the Cancer Genome Atlas-BLCA (TCGA-BLCA) database and the GSE13507 database. Furthermore, 108 BCa patients who received treatment at our institution were subjected to a retrospective analysis. The least absolute shrinkage and selection operator (LASSO) analysis was performed to develop an LLPS-related prognostic signature for BCa. The CCK8, wound healing and Transwell assays were performed. Based on 62 differentially expressed LLPS-related genes (DELRGs), three DELRGs were screened by LASSO analysis including kallikrein-related peptidase 5 (KLK5), monoacylglycerol O-acyltransferase 2 (MOGAT2) and S100 calcium-binding protein A7 (S100A7). Based on three DELRGs, a novel LLPS-related prognostic signature was constructed for individualized prognosis assessment. Kaplan-Meier curve analyses showed that LLPS-related prognostic signature was significantly correlated with overall survival (OS) of BCa. ROC analyses demonstrated the LLPS-related prognostic signature performed well in predicting the prognosis of BCa patients in the training group (the area under the curve (AUC) = 0.733), which was externally verified in the validation cohort 1 (AUC = 0.794) and validation cohort 2 (AUC = 0.766). Further experiments demonstrated that inhibiting KLK5 could affect the proliferation, migration, and invasion of BCa cells. In this study, a novel LLPS-related prognostic signature was successfully developed and validated, demonstrating strong performance in predicting the prognosis of BCa patients.

Construction and verification of an innovative immune-related and hallmark gene sets prognostic model for bladder cancer.

Bladder cancer (BC) is a life-threatening malignancy with high mortality rates. Current prognostic models are insufficient in accurately predicting clinical outcomes, impeding personalized treatment strategies. This study aimed to identify BC subtypes and prognostic gene sets by analyzing changes in immune and hallmark gene sets activity in tumor and adjacent non-tumor tissues to enhance patient outcomes. Utilizing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), gene set variation analysis (GSVA) was applied to C7 immune-related and hallmark gene sets from the Molecular Signatures Database (MSigDB). The CancerSubtype R package was utilized for clustering these gene sets into three categories, from which 109 candidate sets were identified using Venn diagrams. A refined subset of seven gene sets was selected through least absolute shrinkage and selection operator (LASSO) regression for the construction of a risk model. Model validity was confirmed with receiver operating characteristic (ROC) and calibration curves, and a nomogram was constructed to integrate risk scores with clinical parameters. Finally, genes from the gene sets of the model were acquired and analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interactions (PPI) via plugin Molecular Complex Detection (MCODE) and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) in Cytoscape in both tumor and non-tumor tissues. Three BC subtypes were characterized by immunologic and hallmark gene sets, with subtype 1 patients showing worse survival. The prognostic model, based on seven gene sets, effectively stratified risk, with high-risk patients having significantly shorter survival. GO, KEGG, and PPI analyses indicated distinct influences of non-tumor and tumor tissues on the prognosis of BC patients. We constructed and validated a novel prognostic model for risk stratification in BC based on immunologic and hallmark genes sets, which presents a novel perspective on rational treatment approaches and accurate prognostic evaluations for BC by considering both tumor and adjacent non-tumor tissues. This highlights the importance of focusing on alterations in both tumor and adjacent non-tumor tissues, rather than solely on the tumor itself.

The role of deubiquitinase USP2 in driving bladder cancer progression by stabilizing EZH2 to epigenetically silence SOX1 expression

BackgroundThe Ubiquitin-proteasome system (UPS) is known to participate in multiple cellular events. The deubiquitinating enzyme USP2 (ubiquitin-specific protease 2) is involved in the vasculature remodeling process associated with bladder cancer (BLCA). However, the role of USP2 in BLCA progression has not been clearly defined and whether its regulatory mechanism involving EZH2 (Enhancer of Zeste Homolog 2) remains elusive yet. MethodsDifferential expression patterns of USP2 and EZH2 were examined in 46 pairs of BLCA and adjacent normal tissues. USP2 knockdown plasmids were transfected into 5637 and J82 cells to detect its impact on cell proliferation, migration and invasion using CCK-8, EdU, wound healing and transwell assays. The USP2-EZH2-SOX1 cascade was confirmed through Co-immunoprecipitation (Co-IP) and chromatin immunoprecipitation (ChIP) assays. An in vivo verification was conducted using a xenograft model of nude mice. ResultsUSP2 was significantly upregulated in BLCA tissues and cells, which was associated with poor clinical prognosis in BLCA patients. USP2 depletion resulted in decreased cell proliferation, migration and invasion in BLCA cells. USP2 stabilized the EZH2 protein by directly binding to it, thereby reducing its ubiquitination. Ectopic introduction of EZH2 restored cell growth and invasion of BLCA cells, which had been inhibited by USP2 silencing. USP2-mediated stabilization of EZH2 promoted the enrichment of histone H3K27me3 and repression of SOX1. Involvement of the USP2-EZH2-SOX1 axis in tumor formation was ultimately verified in vivo. ConclusionOur findings reveal that a USP2-EZH2-SOX1 axis orchestrates the interplay between dysregulated USP2 and EZH2-mediated gene epigenetic silencing in BLCA progression.

Prognostic value of GARS in bladder cancer and its role in the tumor microenvironment.

Bladder cancer (BC), as a common type of cancer, has a poor prognosis, also some common invasive prognostic or therapeutic markers are difficult to obtain, which makes further treatment of BC difficult. Glycyl-tRNA synthetase (GARS), as one of the aminoacyl-tRNA synthetases that charge tRNAs with their cognate amino acids, has been identified as a target in many diseases, including tumors. Bioassay analysis revealed that GARS was in high expression in most cancer tissues. The expression of GARS gene in BC tissues could assess the prognosis of BC patients, and the expression in urinary extracellular vesicles (uEVs) of patients was positively correlated with the expression in tissues. In addition to this, we analyzed GARS-related differential gene expression, copy number variation (CNV) and mutation profiles, potential biological functions, immune cell infiltration and drug sensitivity. In vivo and vitro tumorigenic experiments were performed to validate the function of GARS. Single-cell data were used to further analyze its role in the microenvironment. In our study, we found that GARS was highly expressed in 30 cancer tissues including BC, and high GARS expression was negatively correlated with the prognosis of BC patients. To address this phenomenon, we analyzed the differential genes between high and low GARS groups by enrichment analysis, and identified the biological signaling pathways that were mainly enriched for their functions, and found that the enrichment was found in immune-related signaling pathways and regulation of cell-cell adhesion. Then we found that GARS was positively associated with immune cell infiltration in BC, and some common immune checkpoints were significantly overexpressed in the GARS-high group. Besides, we found that GARS was enriched in myofibroblasts in the tumor microenvironment, and the enrichment was positively correlated with epithelial-mesenchymal transition (EMT)-related genes. This study also showed a positive correlation between GARS and BC RNA stemness. Patients in the GARS-high group had considerably higher rates of P53 and Titin (TTN) mutations than those in the GARS-low group. Drug Sensitivity analysis screened for drugs that were more sensitive to GARS-high patients. Further, we found that knockdown of GARS significantly inhibited the proliferation, migration and invasion ability both in vivo and in vitro. Finally, we found that in patients with high GARS the expression in uEVs was also at a high level. In summary, this study provided evidence that GARS can be used as a prognostic and therapeutic marker for BC, we can detect GARS in uEVs instead of tissue, to provide a new, simple, noninvasive way to obtain prognostic and therapeutic markers for BC patients.

Identification of bladder cancer subtypes and predictive signature for prognosis, immune features, and immunotherapy based on immune checkpoint genes

Immunotherapy based on immune checkpoint genes (ICGs) has recently made significant progress in the treatment of bladder cancer patients, but many patients still cannot benefit from it. In the present study, we aimed to perform a comprehensive analysis of ICGs in bladder cancer tissues with the aim of evaluating patient responsiveness to immunotherapy and prognosis. We scored ICGs in each BLCA patient from TCGA and GEO databases by using ssGSEA and selected genes that were significantly associated with ICGs scores by using the WCGNA algorithm. NMF clustering analysis was performed to identify different bladder cancer molecular subtypes based on the expression of ICGs-related genes. Based on the immune related genes differentially expressed among subgroups, we further constructed a novel stratified model containing nine genes by uni-COX regression, LASSO regression, SVM algorithm and multi-COX regression. The model and the nomogram constructed based on the model can accurately predict the prognosis of bladder cancer patients. Besides, the patients classified based on this model have large differences in sensitivity to immunotherapy and chemotherapy, which can provide a reference for individualized treatment of bladder cancer.

Status quo and factors of depression and anxiety in patients with non-muscle invasive bladder cancer after plasma electrocision

BACKGROUND Bladder cancer is a type of cancer with a high incidence in men. Plasma electrosurgery (PES) is often used in the treatment of bladder cancer. Postoperative complications often cause depression and anxiety in patients after surgery. AIM To investigate the current state of depression and anxiety after PES in patients with non-muscle-invasive bladder cancer and analyze the factors affecting them. METHODS A retrospective study was conducted to compare the baseline data of patients by collecting their medical history and grouping them according to their mental status into negative and normal groups. Logistic regression analysis was used to explore the risk factors affecting the occurrence of anxiety and depression after surgery in patients with bladder cancer. RESULTS Comparative analyses of baseline differences showed that the patients in the negative and normal groups differed in terms of their first surgery, economic status, educational level, and marital status. A logistic regression analysis showed that it affected the occurrence of anxiety in patients with bladder cancer, and the results showed that whether the risk factors were whether or not it was the first surgery, monthly income between 3000 and 3000-6000, secondary or junior high school education level, single, divorced, and widowed statuses. CONCLUSION The risk factors affecting the onset of anxiety and depression in bladder cancer patients after PES are the number of surgeries, economic status, level of education, and marital status. This study provides a reference for the clinical treatment and prognosis of bladder cancer patients in the future.

Predicting the Prognosis of Bladder Cancer Patients Through Integrated Multi-omics Exploration of Chemotherapy-Related Hypoxia Genes.

Bladder cancer is a prevalent malignancy with high mortality rates worldwide. Hypoxia is a critical factor in the development and progression of cancers. However, whether and how hypoxia-related genes (HRGs) could affect the development and the chemotherapy response of bladder cancer is still largely unexplored. This study comprehensively explored the complex molecular landscape associated with hypoxia in bladder cancer by analyzing 260 hypoxia genes based on transcriptomic and genomic data in 411 samples. Employing the 109 dysregulated hypoxia genes for consensus clustering, we delineated two distinct bladder cancer clusters characterized by disparate survival outcomes and distinct oncogenic roles. We defined a HPscore that was correlated with a variety of clinical features, including TNM stages and pathologic grades. Tumor immune landscape analysis identified three immune clusters and close interactions between hypoxia genes and the various immune cells. Utilizing a network-based method, we defined 129 HRGs exerting influence on apoptotic processes and critical signaling pathways in cancer. Further analysis of chemotherapy drug sensitivity identified potential drug-target HRGs. We developed a Risk Score model that was related to the overall survival of bladder cancer patients based on doxorubicin-target HRGs: ACTG2, MYC, PDGFRB, DHRS2, and KLRD1. This study not only enhanced our understanding of bladder cancer at the molecular level but also provided promising avenues for the development of targeted therapies, representing a significant step toward the identification of effective treatments and addressing the urgent need for advancements in bladder cancer management.

CircPKN2 promotes ferroptosis in bladder cancer by promoting the ubiquitination of Stearoyl-CoA Desaturase 1.

Bladder cancer (BC) is one of the most common malignancies in the male urinary system and currently lacks an optimal treatment strategy. To elucidate the pathogenic mechanisms of BC from the perspective of circular RNAs, we conducted this study. Building upon our previous research, a novel circRNA, circPKN2, captured our interest due to its significant downregulation in BC, and its close association with the prognosis of BC patients. Our research findings indicate that circPKN2 can inhibit the proliferation and migration of BC cells in vitro. Furthermore, we discovered that circPKN2 exerts its anti-cancer effects in BC by promoting ferroptosis. Mechanistic studies revealed that circPKN2 recruits STUB1 to facilitate the ubiquitination of SCD1, thereby suppressing the WNT pathway and promoting ferroptosis in BC. Additionally, our research unveiled the regulatory role of the splicing factor QKI in the biogenesis of circPKN2. Animal studies demonstrated that circPKN2 enhances ferroptosis in BC cells in vivo, inhibiting tumor growth and metastasis. The discovery of the anti-cancer factor circPKN2 holds promise for providing new therapeutic targets in the prevention and treatment of BC.

SLC7A5 correlated with malignancies and immunotherapy response in bladder cancer

BackgroundMetabolic reprogramming contributes to bladder cancer development. This study aimed to understand the role of SLC7A5 in bladder cancer.MethodsWe systematically analyzed the correlation between SLC7A5 and bladder cancer through various approaches, including bioinformatics, western blotting, cell cycle analysis, cell proliferation assays, and invasion experiments. We also investigated the immunological features within the tumor microenvironment (TME), encompassing cancer immune cycles, immune modulators, immune checkpoints, tumor-infiltrating immune cells (TIIC), T cell inflammation scores, and treatment responses. Additionally, for a comprehensive assessment of the expression patterns and immunological roles of SLC7A5, pan-cancer analysis was performed using cancer genomics datasets.ResultsSLC7A5 was associated with adverse prognosis in bladder cancer patients, activating the Wnt pathway and promoting bladder cancer cell cycle progression, proliferation, migration, and invasion. Based on the evidence that SLC7A5 positively correlated with immunomodulators, TIIC, the cancer immune cycle, immune checkpoint and T cell inflammation scores, we also found that SLC7A5 was associated with the inflammatory tumor immune microenvironment. EGFR-targeted therapy, cancer immunotherapy, and radiation therapy were effective for patients with high SLC7A5 expression in bladder cancer. Low SLC7A5 patients were, however, sensitive to targeted therapies and anti-angiogenic therapy, such as blocking β-catenin network, PPAR-γ and FGFR3 signaling. Anti-SLC7A5 combined with cancer immunotherapy may have greater effectiveness than either therapy alone. Furthermore, we observed specific overexpression of SLC7A5 in TME of various cancers.ConclusionSLC7A5 can predict therapeutic response to immunotherapy, radiotherapy and chemotherapy in bladder cancer patients. Targeting SLC7A5 in combination with immunotherapy may be a potentially appropriate treatment option.

Nucleoporin 93 Regulates Cancer Cell Growth and Stemness in Bladder Cancer via Wnt/β-Catenin Signaling.

Bladder cancer (BLCA) is a prevalent cancer type with an unmet need for new therapeutic strategies. Nucleoporin 93 (Nup93) is implicated in the pathophysiology of several cancers, but its relationship with bladder cancer remains unclear. Nup93 expression was analyzed in TCGA datasets and 88 BLCA patient samples. Survival analysis and Cox regression models evaluated the association between Nup93 levels and patient prognosis. BLCA cells were used to investigate the effects of Nup93 overexpression or knockdown on cell growth, invasion, stemness (sphere formation and ALDH2 + cancer stem cell marker), and Wnt/β-catenin signaling in vitro. The Wnt activator BML-284 was used to confirm the involvement of Wnt/β-catenin signaling pathway. A xenograft mouse model validated the in vitro findings. Nup93 was highly expressed in BLCA tissues and cell lines, and high Nup93 expression correlated with poor prognosis in BLCA patients. Nup93 silencing inhibited BLCA cell proliferation, Wnt/β-catenin activation, and cancer cell stemness. Conversely, Nup93 overexpression promoted these effects. BML-284 partially rescued the reduction in cell growth and stemness markers caused by Nup93 knockdown. Nup93 knockdown also suppressed the tumor formation of BLCA cells in vivo. Nup93 regulates BLCA cell growth and stemness via the Wnt/β-catenin pathway, suggesting its potential as a prognostic marker and therapeutic target in BLCA.

CXCL10 could be a prognostic and immunological biomarker in bladder cancer

IntroductionAs proteins that promote immune cell differentiation, chemokines have attracted great interest regarding their role in anti-tumor immune responses within the cancer environment. However, the exact role of CXCL10, a chemokine, in bladder cancer (BLCA) is still not fully elucidated.MethodIn the present study, we employed bioinformatics approaches to examine the expression pattern, prognostic value, and immune infiltration of CXCL10 in BLCA. Furthermore, we focused on examining the impact of CXCL10 on immune therapy in BLCA. Additionally, we validated the expression of CXCL10 in various BLCA cell lines using PCR techniques.ResultsWe observed an upregulation of CXCL10 in BLCA tissues as well as in different cell lines. Additionally, upregulation of CXCL10 indicates a better prognosis for BLCA patients. ESTIMATE and CIBERSORT algorithms suggest that CXCL10 is closely associated with the immune microenvironment of BLCA. Through multiple immune therapy cohorts, we also identified that CXCL10 has shown promising predictive value for assessing the efficacy of immune therapy in in BLCA.ConclusionOur study indicates that CXCL10 has the potential to serve as a favorable prognostic factor and is strongly associated with immune infiltration in BLCA.Graphical

The predictive value of PFKFB3 in bladder cancer prognosis

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase-3 (PFKFB3) influences cancer progression via participating in tumor aerobic glycolysis. In this study, we aimed to evaluate the prognostic significance of PFKFB3 in bladder cancer (BLCA) patients by analyzing a combination of publicly available databases, clinical patient data, and bladder tumor samples from our hospital. Single-cell and bulk RNA-seq data of bladder cancer, obtained from ENA, GEO, and TCGA databases, were utilized for our analysis. The results indicated that PFKFB3 mRNA expression was markedly elevated in bladder cancer compared to paired normal tissue. Furthermore, BLCA patients with high PFKFB3 expression exhibited a significantly worse prognosis (P < 0.05). To validate these findings, clinical data and immunohistochemistry staining were performed on specimens obtained from 89 BLCA patients who underwent radical cystectomy at either Qingdao University Affiliated Hospital or Peking Union Medical College Hospital. The findings from this verification process confirmed that high expression of PFKFB3 serves as a biomarker for predicting worse prognosis in BLCA patients (OR: 2.462, 95 % CI: 1.202–5.042, P = 0.012). To facilitate clinical application, we developed a nomogram based on four variables, including PFKFB3 expression, to predict the survival of BLCA patients. Importantly, this nomogram demonstrated a low mean prediction error of 0.03. Taken together, our findings suggest that PFKFB3 has the potential to serve as both a prognostic biomarker and a therapeutic target for BLCA patients.

A risk model based on lncRNA-miRNA-mRNA gene signature for predicting prognosis of patients with bladder cancer.

We aimed to analyze lncRNAs, miRNAs, and mRNA expression profiles of bladder cancer (BC) patients, thereby establishing a gene signature-based risk model for predicting prognosis of patients with BC. We downloaded the expression data of lncRNAs, miRNAs and mRNA from The Cancer Genome Atlas (TCGA) as training cohort including 19 healthy control samples and 401 BC samples. The differentially expressed RNAs (DERs) were screened using limma package, and the competing endogenous RNAs (ceRNA) regulatory network was constructed and visualized by the cytoscape. Candidate DERs were screened to construct the risk score model and nomogram for predicting the overall survival (OS) time and prognosis of BC patients. The prognostic value was verified using a validation cohort in GSE13507. Based on 13 selected. lncRNAs, miRNAs and mRNA screened using L1-penalized algorithm, BC patients were classified into two groups: high-risk group (including 201 patients ) and low risk group (including 200 patients). The high-risk group's OS time ( hazard ratio [HR], 2.160; 95% CI, 1.586 to 2.942; P= 5.678e-07) was poorer than that of low-risk groups' (HR, 1.675; 95% CI, 1.037 to 2.713; P= 3.393 e-02) in the training cohort. The area under curve (AUC) for training and validation datasets were 0.852. Younger patients (age ⩽ 60 years) had an improved OS than the patients with advanced age (age > 60 years) (HR 1.033, 95% CI 1.017 to 1.049; p= 2.544E-05). We built a predictive model based on the TCGA cohort by using nomograms, including clinicopathological factors such as age, recurrence rate, and prognostic score. The risk model based on 13 DERs patterns could well predict the prognosis for patients with BC.

USP15 facilitates the progression of bladder cancer by amplifying the activation of the NF-κB signaling pathway.

USP15, a pivotal member of the deubiquitinase family, plays a crucial role in orchestrating numerous vital biological processes, including the regulation of NF-κB signaling pathway and deubiquitination of proto-oncogenes. In various cancers, USP15 has been validated to exhibit up-regulated expression, impacting the initiation and progression of cancer. However, its precise mechanism in bladder cancer remains elusive. Our study shed light on the significant overexpression of USP15 in bladder cancer cells compared to normal bladder cells, correlating with a poorer prognosis for bladder cancer patients. Strikingly, attenuation of USP15 expression greatly attenuated the proliferation, migration, and invasion of bladder cancer cells. Moreover, upregulation of USP15 was found to drive cancer progression through the activation of the NF-κB signaling pathway. Notably, USP15 directly deubiquitinates BRCC3, heightening its expression level, and subsequent overexpression of BRCC3 counteracted the antitumoral efficacy of USP15 downregulation. Overall, our findings elucidated the carcinogenic effects of USP15 in bladder cancer, primarily mediated by the excessive activation of the NF-κB signaling pathway, thereby promoting tumor development. These results underscore the potential of USP15 as a promising therapeutic target for bladder cancer in the future.

Comprehensive analysis of scRNA-seq and bulk RNA-seq reveal the characteristics of disulfidptosis and a prognostic signature in BLCA.

Disulfidptosis is a newly discovered mode of cell death. However, its biological mechanism in bladder cancer (BLCA) is still uncharacterized. In this investigation, we firstly examined the expression and mutation of disulfidptosis-related genes (DRGs) in BLCA. Two disulfidptosis phenotypes associated with DRGs expression patterns and immune cell infiltration were built. A disulfidptosis risk score signature was constructed based on ten differentially expressed genes (DEGs) between the disulfidptosis subtypes, which allowed patients to be stratified into high- and low-risk groups. We further confirmed that the disulfidptosis risk score signature has great power to predict prognosis, immune cell infiltration, and immunotherapy efficacy in BLCA. Additionally, we analyzed the differences in therapeutic sensitivities between high- and low-risk groups concerning targeted inhibitor therapy and immunotherapy. Analysis of single-cell RNA sequencing was conducted of the ten hub DRGs. Of the ten genes, we found that DUSP2 and SLCO1B3 were differentially expressed in BLCA tissues and adjacent normal tissues, and were markedly associated with patients' prognosis. Functional experiments revealed that overexpression of DUSP2 or knockdown of SLCO1B3 significantly inhibited cell proliferation, migration, and invasion in BLCA cells. In all, we present a fresh disulfidptosis-related prognostic signature, which has a remarkable capacity to characterize the immunological landscape and prognosis of BLCA patients.

Identification of Hydroxysteroid Dehydrogenase Type 1 As a Potential Bladder Tumor Marker.

The 17beta-hydroxysteroid dehydrogenase type 1 (HSD17B) family has been implicated in the prognosis and treatment prediction of various malignancies; however, its association with bladder cancer (BLCA) remains unclear. This study aimed to evaluate the potential of HSD17B1, as a prognostic biomarker, for the survival of patients with BLCA and to determine its effectiveness as a supplemental biomarker for BLCA. A series of bioinformatics techniques were applied to investigate the expression of HSD17B1 in different types of cancer and its potential association with the prognosis of BLCA patients using diverse databases. The UALCAN, Human Protein Atlas, cBioPortal, Metascape, GEPIA, MethSurv, and TIMER were employed to analyze expression differences, mutation status, enrichment analysis, overall survival, methylation, and immune-infiltrating cells. The real-time reverse transcription-PCR (qRT-PCR) was implemented to detect the messenger ribonucleic acid (mRNA) expression levels of HSD17B1 in vitro. Elevated mRNA and protein levels of HSD17B1, surpassing normal levels, were observed in BLCA samples. In addition, the BLCA patients with higher mRNA expression level of HSD17B1 significantly reduced the overall survival. Also, several immune infiltrating cells, including mast cell resting CIBERSORT-ABS, have been identified as tumor-associated biomarker genes, with the potential to significantly influence the immunological environment. Finally, qRT-PCR analysis revealed a significant upregulation of HSD17B1 mRNA expression level in the cancer cells compared to the human 293T cells, which was consistent with the bioinformatics data. There is a strong correlation between the elevated HSD17B1 expression and positive prognosis in patients with BLCA. Therefore, HSD17B1 can be used as a prognostic biomarker in these patients.