m6A reader IGF2BP2 promotes M2 macrophage polarization and malignant biological behavior of bladder cancer by stabilizing NRP1 mRNA expression.

BACKGROUND: Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been confirmed to play oncogenic role in many cancers. However, the role and mechanism of IGF2BP2 in bladder cancer (BCa) still deserves to be further revealed. METHODS: The mRNA and protein levels of IGF2BP2 and neuronilin-1 (NRP1) were detected by real-time quantitative PCR (RT-qPCR) and western blot. Cell proliferation, apoptosis, migration and invasion were determined using colony formation assay, EdU assay, CCK8 assay, flow cytometry and transwell assay. Xenograft tumor model was conducted to evaluate the role of IGF2BP2 in vivo. THP-1-M0 macrophages were co-cultured with the condition medium (CM) of BCa cells to induce polarization. M2 macrophage polarization was assessed by detecting the mRNA levels of M2 macrophage markers using RT-qPCR and measuring the proportion of M2 macrophage markers using flow cytometry. Moreover, MeRIP and RIP assay were performed to assess m6A level and the interaction between IGF2BP2 and NRP1. RESULTS: IGF2BP2 and NRP1 were upregulated in BCa tissues and cells. IGF2BP2 knockdown suppressed BCa cell growth and metastasis, as well as inhibited BCa tumor growth. After THP-1-M0 macrophages were co-cultured with the CM of BCa cells, the levels of M2 macrophage markers were markedly enhanced, while this effect was abolished by IGF2BP2 knockdown. IGF2BP2 level was positively correlated with NRP1 level, and it could increase NRP1 mRNA stability. NRP1 overexpression reversed the suppressive effect of IGF2BP2 knockdown on M2 macrophage polarization and BCa cell progression. CONCLUSION: m6A-reader IGF2BP2 enhanced M2 macrophage polarization and BCa cell progression by promoting NRP1 mRNA stability.

Comparative efficacy of palliative radiotherapy dose schedules in advanced bladder cancer-associated gross hematuria.

Introduction: Gross hematuria (GH) in advanced/inoperable bladder cancer patients causes significant morbidity. Patients frequently need multiple transfusions. Hypofractionated radiotherapy (RT) has been shown to be effective in symptom palliation. In this study, we explore the efficacy of various fractionation regimens in these patients. Methods: This single institute retrospective analysis was conducted on 60 consecutive patients treated with palliative RT. Fractionation (single versus multiple) and biologically equivalent doses (BED; high ≥36 Gy versus low <36 Gy) were used to compare the efficacy of various fractionation regimens. The primary outcome was the difference in objective response rate (ORR) between various strata at 2, 4, 8 and 12 weeks. Major secondary outcomes were differences in ORR according to Eastern Cooperative Oncology Group (ECOG) performance status (PS) and tumour node metastases (TNM) stage, and the proportion of patients requiring re-transfusion(s) at 12 weeks. Data were analysed using SPSS 23. Results: Overall ORR at 2, 4, 8 and 12 weeks was 86%, 77%, 67% and 55%, respectively. There was no statistically significant difference in response rates between single or multi-fraction, or high versus low BED groups (All p = >0.05). Moreover, ECOG PS (p = 0.11) or TNM stage (p = 0.58) also had no impact on the response rate at 12 weeks. Nearly one-third (31%) of patients required further transfusions at 12 weeks. Conclusion: RT is an effective modality to control GH. No difference in ORR was found between single fractions versus multiple fractions, or high versus low BED regimens. Single fraction RT can be offered to these patients considering low cost, patient convenience and minimal side effects.

Comparison of staging MRI to re-resection for localised bladder cancer: Narrative review.

Introduction: Bladder cancer (BCa) is characterised by high prevalence, multifocality, and frequent recurrence, imposing significant clinical and economic burdens. Accurate staging, particularly distinguishing non-muscle-invasive bladder cancer (NMIBC) from muscle-invasive bladder cancer (MIBC) disease, is crucial for guiding treatment decisions. This narrative review explores the potential implications of incorporating multiparametric magnetic resonance imaging (mpMRI) and the Vesical Imaging Reporting Data System (VI-RADS) into BCa staging, focusing on repeat transurethral resection of bladder tumour (re-TURBT). Methods: A comprehensive search of PubMed, EMBASE, and MEDLINE databases identified studies published from 2018 to 2023 discussing mpMRI or VI-RADS in the context of re-TURBT for BCa staging. Studies meeting inclusion criteria underwent qualitative analysis. Results: Six recent studies met inclusion criteria. VI-RADS scoring, accurately predicted muscle invasion, aiding in NMIBC/MIBC differentiation. VI-RADS scores of ≥3 indicated MIBC with high sensitivity and specificity. VI-RADS potentially identified patients benefiting from re-TURBT and those for whom it could be safely omitted. Discussion: mpMRI and VI-RADS offer promising prospects for BCa staging, potentially correlating more closely with re-TURBT and radical cystectomy histopathology than initial TURBT. However, validation and careful evaluation of clinical integration are needed. Future research should refine patient selection and optimise mpMRI's role in BCa management. Conclusion: VI-RADS scoring could revolutionise BCa staging, especially regarding re-TURBT. There is potential that VI-RADS correlates more with the histopathology of re-TURBT and radical cystectomy than initial TURBT. While promising, ongoing research is essential to validate utility, refine selection criteria, and address economic considerations. Integration of VI-RADS into BCa staging holds potential benefits for patients and health care systems.

Understanding symptom contribution to sex inequality in bladder and renal cancer stage at diagnosis.

Background: Understanding sex-specific factors contributing to advanced-stage diagnosis can guide interventions to reduce sex inequality in patients with urological cancers. Method: We used linked primary care and cancer registry data to examine associations between symptoms and advanced-stage in 1151 bladder cancer and 440 renal cancer patients diagnosed between January 2012 and December 2015 in England. We performed logistic regression, adjusting for sex, age, deprivation and routes to diagnosis, including interaction terms between symptoms and sex and symptoms and age. Results: Female sex (OR vs. men 1.89 [1.28-2.79]; p = 0.001) and patients presenting with urinary tract infections (OR 2.22 [1.34-3.69]) and abdominal symptoms (OR 2.19 [1.30-3.70]) were associated with increased odds of advanced-stage bladder cancer (vs. haematuria, p = 0.016 for both). Women with haematuria and men with abdominal symptoms (compared with the opposite sex with the same presenting symptom) were more likely to have advanced-stage bladder cancer. Neither sex nor symptom associations were observed for renal cancer. Conclusion: Non-haematuria symptoms are associated with higher risk of advanced-stage bladder cancer. Greater risk of advanced-stage bladder cancer in women may reflect biological differences in haematuria onset and sex differences during diagnostic process. Identifying higher risk women with haematuria may reduce sex inequalities in bladder cancer outcomes.

Ureteroenteric strictures after cystectomy: Side-specific risk factors and radiological assessment.

Objective: To evaluate risk factors contributing to side-specific benign ureteroenteric strictures following radical cystectomy with an ileal conduit. Materials and Methods: Data obtained from patients with bladder cancer who underwent radical cystectomy with ileal conduit surgery between 2015 and 2018 were retrospectively analysed. Imaging prior to surgery was analysed, regarding calcifications in the aorta, sarcopenia and postoperatively for length of remaining left ureter. Descriptive analyses were performed on preoperative and perioperative data, comparing patients who developed unilateral left- or right-sided strictures, bilateral strictures, to those who remained free of strictures. COX regression analysis was employed to calculate crude and adjusted hazard ratio for side-specific strictures. Results: The study included 395 patients. Strictures developed in 19% (75/395) of the patients, within a median period of 9 months: 57% (43/75) unilateral left sided, 20% (15/75) unilateral right sided and 23% (17/75) bilateral. Unilateral left-sided stricture was associated with higher body mass index (p = 0.077) and hypercholesterolemia (p = 0.007). Right-sided stricture was associated with a history of prior abdominal surgery (p = 0.029) and postoperative leakage (p = 0.004). Bilateral stricture was associated with smoking (p = 0.006) and high BMI (p = 0.015). The adjusted HR comparing patients with and without previous abdominal surgery was only significantly higher for right-sided ureteroenteric strictures (HR 3.18 [95% CI: 1.11; 9.05]) compared with patients without strictures. No association was identified between strictures and preoperative aortic calcification of the abdominal aorta or sarcopenia as estimated from imaging. Conclusion: The aetiology of ureteroenteric strictures appears multifactorial. Our findings suggest that development of left-sided stricture is influenced by factors associated with metabolic syndrome, indicating a potential role of distal ureteric ischemia. On the other hand, right-sided stricture was more frequent in patients with previous abdominal surgery and postoperative leakage.

Identification of macrophage-related genes in bladder cancer patients using single-cell sequencing and construction of a prognostic model.

Single-cell sequencing is an emerging technology that can effectively identify cell types in tumors. In the tumor microenvironment of bladder cancer, macrophages play a crucial role in invasion and immune escape. This study aimed to assess the expression of macrophage-related genes (MRGs) in the tumor microenvironment of bladder cancer patients and construct a prognostic model based on MRGs using bioinformatics methods. METHODS: Single-cell sequencing data from bladder cancer patients was downloaded from the GEO. After quality control and cell type identification, macrophages in the samples were extracted for re-clustering. Feature genes were then identified, and MRGs were assessed. Genetic data from TCGA database bladder cancer patients was also downloaded and organized. The intersection of MRGs and the TCGA gene set was determined. Clinical information was connected with this intersection, and the data was divided into training and validation sets. The training set was used for model construction and the validation set for model verification. A prognostic model based on MRGs was built using the LASSO algorithm and Cox regression. Patients were divided into high-risk and low-risk groups based on their prognostic features, and survival information in the training and validation sets was observed. The predictive ability of the model was assessed using a ROC curve, followed by a calibration plot to predict 1-, 3-, and 5-year survival rates. RESULTS: Four cell types were identified, and after extracting macrophages, three cell subgroups were clustered, resulting in 1,078 feature genes. The top 100 feature genes from each macrophage subgroup were extracted and intersected with TCGA expressed genes to construct the model. A risk prediction model composed of CD74, METRN, PTPRR, and CDC42EP5 was obtained. The survival and ROC curves showed that this model had good predictive ability. A calibration curve also demonstrated good prognostic ability for patients. CONCLUSION: This study, based on single-cell data, TCGA data, and clinical information, constructed an MRG-based prognostic model for bladder cancer using multi-omics methods. This model has good accuracy and reliability in predicting the survival and prognosis of patients with bladder cancer, providing a reference for understanding the interaction between MRGs and bladder cancer.

Digital volumetric assessment of CIS and tumor mass compliments conventional histopathological assessment in muscle-invasive urothelial bladder cancer.

Carcinoma in situ (CIS) of the bladder is a known parameter regarding the prognosis and recurrence tendency of urothelial carcinomas. Nevertheless, there is little evidence whether the amount of CIS or other precursor lesions, as well as the quantified tumor mass of muscle-invasive urothelial carcinoma, has an influence on the survival or recurrence rate of affected patients. From 80 patients with muscle invasive urothelial bladder cancer and radical cystectomy, 23 samples each were obtained as part of a whole organ mapping in a single institution study, in which the precursor lesions and tumor area were digitally measured and further correlated to pathological standard parameters, patient survival, molecular luminal and basal subtypes, and immune infiltration. Significant correlations were found between tumor mass and surface lining CIS amount for pT-stage, lymphovascular invasion, and perineural infiltration. Furthermore, an increased tumor mass as well as an increased amount of CIS combined with an increased tumor mass showed a significantly reduced survival rate in multivariable analysis (HR = 2.75; P = 0.019 vs. HR = 3.54; P = 0.002) as well as a significantly increased recurrence. No correlations could be found with molecular subtypes and immune infiltration. The exact measurement of the tumor mass with and without the CIS surface area, whether manually or, more specifically, digitally, could be incorporated into routine diagnostics and implemented as an independent predictor for patient post-surgical outcomes. It can therefore serve as an additional predictor for risk stratification and, if necessary, intensified follow-up care or therapy.

Giant cell carcinoma of the urinary bladder : Clinicopathologic analysis and oncological outcomes.

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60-90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50-90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates.

Network Pharmacology Combined with Bioinformatics Analysis to Texplore the Potential Mechanism of Phellodendri Chinensis Cortex Against Bladder Cancer.

The pharmacological mechanism of Phellodendri Chinensis cortex (PCC) against diseases, especially bladder cancer (BC), has never been reported systematically. This study was designed to explore potential mechanism of PCC in treatment of BC. First, we used network pharmacology to discover the potential mechanism of Phellodendri Chinensis cortex and phellodendrine against bladder cancer. Then, we used bioinformatics analysis to verify the correlation between gene expression analysis, survival analysis and common targets. Finally, molecular docking was used to calculate the binding energies of phellodendrine and common targets.A total of 264 targets for PCC were predicted, and 391 BC-related targets were obtained from 4 databases. There were 54 potential targets, 315 biological processes, and 120 signaling pathways involved for PCC against BC. The CDKN2A expression increased and the ESR1, JUN, IL6, AR, and PTGS2 levels decreased in BC according to Gene Expression Profiling Interactive Analysis version 2. The high expression of JUN, MYC, EGFR, and EGF and low expression of VEGFA and PPARG were associated with short overall survival (OS). The high expression of AKT1, EGFR, and EGF and low expression of IL1ß were associated with poor disease-free survival (DFS). The search of the intersection of phellodendrine and BC targets yielded 11 common targets, 50 biological processes, and 13 signaling pathways involved. High AURKA and FASN and low ESR1, JUN, ABCB1, and PTGS1 were expressed in BC. The high expression of FASN, ABCC1, PTGS1, JUN, and PIK3CA was associated with short OS, the high expression of PIK3CA and ABCC1 was associated with poor DFS prognosis. Phellodendrine showed a better binding affinity for PTGS2 protein with a docking score of -7.183 and a MM-GBSA result of -46.47 kcal/mol. This study revealed potential mechanism of PCC and phellodendrine against BC through network pharmacology and bioinformatics.

ZDHHC9-mediated Bip/GRP78 S-palmitoylation inhibits unfolded protein response and promotes bladder cancer progression.

Recent studies have highlighted palmitoylation, a novel protein post-translational modification, as a key player in various signaling pathways that contribute to tumorigenesis and drug resistance. Despite this, its role in bladder cancer (BCa) development remains inadequately understood. In this study, ZDHHC9 emerged as a significantly upregulated oncogene in BCa. Functionally, ZDHHC9 knockdown markedly inhibited tumor proliferation, promoted tumor cell apoptosis, and enhanced the efficacy of gemcitabine (GEM) and cisplatin (CDDP). Mechanistically, SP1 was found to transcriptionally activate ZDHHC9 expression. ZDHHC9 subsequently bound to and palmitoylated the Bip protein at cysteine 420 (Cys420), thereby inhibiting the unfolded protein response (UPR). This palmitoylation at Cys420 enhanced Bip's protein stability and preserved its localization within the endoplasmic reticulum (ER). ZDHHC9 might become a novel therapeutic target for BCa and could also contribute to combination therapy with GEM and CDDP.

Nano-Bacillus Calmette-Guérin immunotherapies for improved bladder cancer treatment. / çº³ç±³å¡ä»‹è‹—æ”¹å–„è†€èƒ±ç™Œçš„å ç–«æ²»ç–—æ•ˆæžœ.

Cancer immunotherapy has rapidly become the fourth mainstream treatment alternative after surgery, radiotherapy, and chemotherapy, with some promising results. It aims to kill tumor cells by mobilizing or stimulating cytotoxic immune cells. However, the clinical applications of tumor immunotherapies are limited owing to a lack of adequate delivery pathways and high toxicity. Recently, nanomaterials and genetic engineering have shown great potential in overcoming these limitations by protecting the delivery of antigens, activating targeted T cells, modulating the immunosuppressive tumor microenvironment, and improving the treatment efficacy. Bacillus Calmette-Guérin (BCG) is a live attenuated Mycobacterium bovis vaccine used to prevent tuberculosis, which was first reported to have antitumor activity in 1927. BCG therapy can activate the immune system by inducing various cytokines and chemokines, and its specific immune and inflammatory responses exert antitumor effects. BCG was first used during the 1970s as an intravesical treatment agent for bladder cancer, which effectively improved immune antitumor activity and prevented tumor recurrence. More recently, nano-BCG and genetically engineered BCG have been proposed as treatment alternatives for bladder cancer due to their ability to induce stronger and more stable immune responses. In this study, we outline the development of nano-BCG and genetically engineered BCG for bladder cancer immunotherapy and review their potential and associated challenges.

Carboxylated mesoporous silica nanoparticle-nucleic acid chimera conjugate-assisted delivery of siRNA and doxorubicin effectively treat drug-resistant bladder cancer.

Chemotherapy is the main treatment for bladder cancer, but drug resistance and side effects limit its application and therapeutic effect. Herein, we constructed doxorubicin (DOX)/COOH-mesoporous silica nanoparticle/polyethylenimine (PEI)/nucleic acid chimeras (DOX/MSN/Chimeras) to reduce the toxicity of chemotherapy drugs and the resistance of bladder cancer cells. Transmission electron microscopy showed that PEI was coated on the DOX/MSN/BSA nanoparticles with a diameter of about 150 nm. DOX/MSN/PEI could control DOX release for over 48 h, and the sudden release rate was significantly lower than DOX/MSN. Immunohistochemical results showed that DOX/MSN/Chimera specifically bound to bladder cancer cells, and markedly inhibited PI3K expression and proliferation of DOX-resistant bladder cancer cells. DOX/MSN/Chimera promoted the apoptosis of drug-resistant bladder cancer cells, which was superior to DOX/MSN/Aptamer or DOX/MSN. We further carried out animal experiments and found that DOX/MSN/Chimera could reduce the volume of transplanted tumors in vivo. Compared with DOX/MSN/Aptamer group, the proliferation rate was significantly decreased and the proportion of apoptotic cells was highly increased. Through the histological observation of kidneys and lungs, we believed that DOX/MSN/Chimera can effectively reduce the damage of chemotherapy drugs to normal tissues. In conclusion, we constructed a COOH-MSN/nucleic acid chimera conjugate for the targeted delivery of siRNA and anti-cancer drugs. Our study provides a new method for personalized and targeted treatment of drug-resistant bladder cancer.

Prolonged Response to Osimertinib in EGFR-Mutated Metastatic Urothelial Carcinoma, a Case Report.

A 48-year-old woman without obvious environmental risk factors was diagnosed with metastatic urothelial carcinoma harboring a mutation in EGFR typical of driver mutations for non-small cell lung cancer. Within a year, her cancer progressed on four standard therapies for urothelial cancer, including cancer in lungs, liver, bone, and brain. As fifth-line therapy, she received osimertinib, leading to a complete response in the brain and improvement elsewhere, and the cancer remained controlled for six months. Targeted therapy for rare driver mutations can be effective in urothelial cancer and should be considered prior to exhausting standard therapies.

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

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Effect of Bacille Calmette-Guérin for Non-Muscle-Invasive Bladder Cancer After Prostate Radiotherapy.

BACKGROUND: Little is known about the impact of prior prostate radiation therapy (RT) on the Bacille Calmette-Guerin (BCG) immunotherapy response in patients with non-muscle invasive bladder cancer (NMIBC). OBJECTIVE: We hypothesized that the damaging radiation effects on the bladder could negatively influence BCG efficacy. METHODS: Men with a history of high-risk NMIBC were identified within the Surveillance, Epidemiology, and End Results-Medicare database. All patients completed adequate BCG defined as at least 5 plus 2 treatments completed within 12 months. Patients were stratified into 2 groups: with prior RT for prostate cancer and without prior RT before the diagnosis of NMIBC. The primary endpoint was a 5-year composite for progression defined as disease progression requiring systemic chemotherapy, checkpoint inhibitors, radical or partial cystectomy, or cancer-specific death. RESULTS: We identified 3,466 patients with NMIBC, including 145 with prior RT for prostate cancer. Five-year progression occurred in 471 patients (13.6%). Patients with prior RT were older than patients without prior RT (77.0 vs 75.0 years; P < .001). The distribution of T stage was significantly different at diagnosis between the RT and non-RT groups (RT: Ta, 44.8%; Tis, 18.6%; T1, 36.6%; without RT: Ta, 40.9%; Tis, 10.8%; T1, 48.3%; P = .002). No difference in the risk of total progression was observed between patients with and without prior RT (P = .67). Similarly, no difference was observed after multivariable adjustment (hazard ratio, 0.99; 95% CI, 0.61-1.58; P = .95). CONCLUSION: For patients with NMIBC who undergo adequate BCG treatment, prior RT for prostate cancer was not associated with worse 5-year progression-free survival.

PTBP1-mediated biogenesis of circATIC promotes progression and cisplatin resistance of bladder cancer.

Background: Cisplatin (DDP) based combination chemotherapy is a vital method for the treatment of bladder cancer (BLca). Chemoresistance easily occurs in the course of cisplatin chemotherapy, which is one of the important reasons for the unfavorable prognosis of BLca patients. Circular RNAs (circRNAs) are widely recognized for their role in the development and advancement of BLca. Nevertheless, the precise role of circRNAs in DDP resistance for BLca remains unclear. Methods: To study the properties of circATIC, sanger sequencing, agarose gel electrophoresis and treatment with RNase R/Actinomycin D were utilized. RT-qPCR assay was utilized to assess the expression levels of circRNA, miRNA and mRNA in BLca tissues and cells. Functional experiments were conducted to assess the function of circATIC in BLca progression and chemosensitivity in vitro. Various techniques such as FISH, Dual-luciferase reporter assay, TRAP, RNA digestion assay, RIP and ChIRP assay were used to investigate the relationships between PTBP1, circATIC, miR-1247-5p and RCC2. Orthotopic bladder cancer model, xenograft subcutaneous tumor model and xenograft lung metastasis tumor model were performed to indicate the function and mechanism of circATIC in BLca progression and chemosensitivity in vivo. Results: In our study, we observed that circATIC expression was significantly enhanced in BLca tissues and cells and DDP resistant cells. Patients with higher circATIC expression have larger tumor diameter, higher incidence of postoperative metastasis and lower overall survival rate. Further experiments showed that circATIC accelerated BLca cell growth and metastasis and induced DDP resistance. Mechanistically, alternative splicing enzyme PTBP1 mediated the synthesis of circATIC. circATIC could enhance RCC2 mRNA stability via sponging miR-1247-5p or constructing a circATIC/LIN28A/RCC2 RNA-protein ternary complex. Finally, circATIC promotes RCC2 expression to enhance Epithelial-Mesenchymal Transition (EMT) progression and activate JNK signal pathway, thus strengthening DDP resistance in BLca cells. Conclusion: Our study demonstrated that circATIC promoted BLca progression and DDP resistance, and could serve as a potential target for BLca treatment.

PA-MSHA improves prognosis of patients undergoing radical cystectomy: a retrospective cohort study using inverse probability of treatment weighting.

Objective: To observe the effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on the prognosis and the incidence of lymphatic leakage in patients undergoing radical cystectomy (RC). Method: A total of 129 patients who underwent RC in Lanzhou University Second Hospital from 2013 to 2022 were enrolled in this study. They were divided into 43 patients treated with PA-MSHA and 86 patients in the control group. Inverse probability of treatment weighting (IPTW) was applied to reduce potential selection bias. Kaplan-Meier method and Cox regression analysis were used to analyze the effect of PA-MSHA on the survival of patients and the incidence of postoperative lymphatic leakage. Results: The PA-MSHA group exhibited improved overall survival (OS) and cancer-specific survival (CSS) rates compared to the control group. The 3-year and 5-year overall survival (OS) rates for the PA-MSHA group were 69.1% and 53.2%, respectively, compared to 55.6% and 45.3% for the control group (Log-rank=3.218, P=0.072). The 3-year and 5-year cancer-specific survival (CSS) rates for the PA-MSHA group were 73.3% and 56.5%, respectively, compared to 58.0% and 47.3% for the control group (Log-rank=3.218, P=0.072). Additionally, the 3-year and 5-year progression-free survival (PFS) rates for the PA-MSHA group were 74.4% and 56.8%, respectively, compared to 57.1% and 52.2% for the control group (Log-rank=2.016, P=0.156). Multivariate Cox regression analysis indicates that lymph node metastasis and distant metastasis are poor prognostic factors for patients, while the use of PA-MSHA can improve patients' OS (HR: 0.547, 95%CI: 0.304-0.983, P=0.044), PFS (HR: 0.469, 95%CI: 0.229-0.959, P=0.038) and CSS (HR: 0.484, 95%CI: 0.257-0.908, P=0.024). The same trend was observed in the cohort After IPTW adjustment. Although there was no significant difference in the incidence of postoperative lymphatic leakage [18.6% (8/35) vs. 15.1% (84.9%), P=0.613] and pelvic drainage volume [470 (440) ml vs. 462.5 (430) ml, P=0.814] between PA-MSHA group and control group, PA-MSHA could shorten the median retention time of drainage tube (7.0 d vs 9.0 d) (P=0.021). Conclusion: PA-MSHA may improve radical cystectomy in patients with OS, PFS, and CSS, shorten the pelvic drainage tube retention time.

Prediction of immunotherapy response of bladder cancer with a pyroptosis-related signature indicating tumor immune microenvironment.

Background: Although prognostic models based on pyroptosis-related genes (PRGs) have been constructed in bladder cancer (BLCA), the comprehensive impact of these genes on tumor microenvironment (TME) and immunotherapeutic response has yet to be investigated. Methods: Based on expression profiles of 52 PRGs, we utilized the unsupervised clustering algorithm to identify PRGs subtypes and ssGSEA to quantify immune cells and hallmark pathways. Moreover, we screened feature genes of distinct PRGs subtypes and validated the associations with immune infiltrations in tissue using the multiplex immunofluorescence. Univariate, LASSO, and multivariate Cox regression analyses were employed to construct the scoring scheme. Results: Four PRGs clusters were identified, samples in cluster C1 were infiltrated with more immune cells than those in others, implying a favorable response to immunotherapy. While the cluster C2, which shows an extremely low level of most immune cells, do not respond to immunotherapy. CXCL9/CXCL10 and SPINK1/DHSR2 were identified as feature genes of cluster C1 and C2, and the specimen with high CXCL9/CXCL10 was characterized by more CD8 + T cells, macrophages and less Tregs. Based on differentially expressed genes (DEGs) among PRGs subtypes, a predictive model (termed as PRGs score) including five genes (CACNA1D, PTK2B, APOL6, CDK6, ANXA2) was built. Survival probability of patients with low-PRGs score was significantly higher than those with high-PRGs score. Moreover, patients with low-PRGs score were more likely to benefit from anti-PD1/PD-L1 regimens. Conclusion: PRGs are closely associated with TME and oncogenic pathways. PRGs score is a promising indicator for predicting clinical outcome and immunotherapy response.

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.

Association of interleukin6 rs1800796 gene polymorphism and serum level with bladder cancer in Egyptian population.

BACKGROUND: Urinary bladder cancer (UBC)is a common tumor of the urinary tract. OBJECTIVES: To assess the diagnostic significance of IL6 rs1800796 gene polymorphism and IL6 serum level among Egyptian patients with UBC. DESIGN AND METHODS: One hundred patients with UBC were selected from the Mansoura Urology and Nephrology Center, in addition to 100 healthy control subjects; using PCR and ELISA techniques for IL6 detection. RESULTS: The rs1800796 GC, CC genotypes, and C allele were significantly more prevalent in the cases with bladder cancer compared to the healthy group (p < 0.001, = 0.021, < 0.001 respectively). There was a clear association between elevated levels of IL6 and bladder cancer versus the control group (median = 4.2, 0.89 respectively, p < 0.001). Serum IL6 levels showed significantly higher levels in patients carrying CC, followed by GC then GG genotypes. No significant association was found between IL6 rs1800796 gene polymorphism or serum level with demographic or laboratory data. CONCLUSION: It is suggested that there is a clear link between elevated IL6 levels as well as IL6 rs1800796 gene polymorphism with bladder cancer, suggesting their potential utility as biomarkers for the disease.