Integrating oxidative-stress biomarkers into a precision oncology risk-stratification model for bladder cancer prognosis and therapy.

Introduction: Bladder cancer is a common malignant tumor with significant heterogeneity, making personalized risk stratification crucial for optimizing treatment and prognosis. This study aimed to develop a prognostic model based on oxidative stress-related genes to guide risk assessment in bladder cancer. Methods: Differentially expressed oxidative stress-related genes were identified using the GEO database. Functional enrichment and survival analyses were performed on these genes. A risk-scoring model was built and tested for prognostic value and therapeutic response prediction. Expression of key genes was validated by qRT-PCR in samples from two muscle-invasive and two non-muscle-invasive bladder cancer patients. Results: Several oxidative stress-related genes were identified as significantly associated with survival. The risk-scoring model stratified patients into high- and low-risk groups, accurately predicting prognosis and therapeutic responses. qRT-PCR confirmed the differential expression of key genes in patient samples. Discussion: The study provides a concise risk stratification model based on oxidative stress-related genes, offering a practical tool for improving personalized treatment in bladder cancer. Further validation is required for broader clinical application.

Revealing the mechanisms of RAC3 in tumor aggressiveness, the immunotherapy response, and drug resistance in bladder cancer.

Background: Bladder cancer (BLCA) is a prevalent urinary tract malignancy with a high propensity for recurrence and chemoresistance. The molecular mechanisms underlying its progression and response to therapy have not been fully elucidated. Methods: We conducted a multifaceted analysis, integrating immunohistochemical (IHC) staining, bioinformatics evaluation using TCGA and CCLE databases, and in vitro assays using the BLCA cell lines 5637 and T24. RAC3 expression was assessed relative to clinical and pathological features. Functional enrichment analyses and gene set enrichment analysis (GSEA) were performed to identify associated biological processes and pathways. The impacts of RAC3 on cell proliferation, migration, invasion, and the immune microenvironment were evaluated using siRNA knockdown, CCK-8, Transwell, wound healing and colony formation assays. Results: Elevated RAC3 expression was significantly correlated with an advanced tumor stage, lymph node metastasis, and poor prognosis for BLCA patients. The functional enrichment analysis implicated RAC3 in immune cell infiltration and immune checkpoint mechanisms. Notably, RAC3 knockdown significantly reduced the proliferative, migratory, and invasive capabilities of BLCA cells. These effects were reversed by the overexpression of RAC3. Additionally, RAC3 expression was linked to chemoresistance, with high RAC3 expression predicting resistance to certain therapeutic agents. The TIDE algorithm indicated that RAC3 expression could be a predictive biomarker for the immunotherapy response. Conclusion: RAC3 was identified as a potential therapeutic target and biomarker of BLCA, as its expression significantly influenced tumor progression, the immune response, and chemosensitivity. Targeting RAC3 may provide a novel strategy for the management of BLCA, particularly for patients resistant to conventional therapies. Further research is essential to elucidate the detailed mechanisms of RAC3 in BLCA and explore its clinical application in precision medicine.

Emerging molecular therapies in the treatment of bladder cancer.

Bladder cancer is a leading cancer type in men. The complexity of treatment in late-stage bladder cancer after systemic spread through the lymphatic system highlights the importance of modulating disease-free progression as early as possible in cancer staging. With current therapies relying on previous standards, such as platinum-based chemotherapeutics and immunomodulation with Bacillus Calmette-Guerin, researchers, and clinicians are looking for targeted therapies to stop bladder cancer at its source early in progression. A new era of molecular therapies that target specific features upregulated in bladder cancer cell lines is surfacing, which may be able to provide clinicians and patients with better control of disease progression. Here, we discuss multiple emerging therapies including immune checkpoint inhibitors of the programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway, antibody-drug conjugates, modulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) cell proliferation pathway, chimeric antigen receptor T-cell therapy, and fibroblast growth factor receptor targeting. Together, these modern treatments provide potentially promising results for bladder cancer patients with the possibility of increasing remission and survival rates.

A Single Institution Experience in the Management of Localized Neuroendocrine Carcinoma of the Bladder.

BACKGROUND: Neuroendocrine carcinoma of the bladder (NEC-bladder) is a rare disease with poor outcomes and variable treatment approaches. MATERIALS AND METHODS: Patients with localized NEC-bladder treated with surgery or radiation between 2001-2021 were retrospectively identified. Rates of pathologic complete response (pCR) and downstaging were evaluated following NAC in surgically-treated patients. Progression-free survival (PFS) and overall survival (OS) were analyzed with univariable (log-rank) and multivariable (MVA; Cox regression) methods. RESULTS: Sixty-five patients were identified having a median age of 73. The tumor histology distribution was small cell (64.6%) or urothelial with NE differentiation (35.4%). Most patients (69.2%) received NAC. Patients received local therapy by surgery (78.5%) or chemoradiation (21.5%). The majority (62.7%) of surgical patients had ≥ pT2 with 37.3% having nodal involvement (pN+). The pCR and downstaging rates were 21.6% and 35.1%, respectively. At a median follow-up of 60 months (m), the median PFS and OS were 16.4m and 25.9m, respectively. NAC improved PFS (p=0.04) and downstaging improved PFS (p=0.012) and OS (p<0.001). Patients receiving NAC with ypN0 vs. ypN+ had median OS of 69.9m vs 15.3m, respectively (p<0.001). MVA identified receipt of NAC and pN as predictors of PFS; pN was predictive of OS. No differences in PFS or OS were seen between histology of primary tumor. The brain metastasis rate was 10.8% with all patients having small cell histology. CONCLUSIONS: Optimized therapy in NEC-bladder includes NAC followed by local consolidation. Ascertainment of ypN0 is associated with long term survival, while pN+ remains associated with poor outcomes.

Prognostic Impact of Bone Metastasis in Patients With Metastatic Urothelial Carcinoma Treated With Durvalumab With or Without Tremelimumab in the DANUBE Study.

INTRODUCTION: Bone metastases (BM) in metastatic urothelial carcinoma (mUC) may impact patient outcomes, but their independent effect with immune checkpoint inhibitors (ICIs) is uncertain. We aimed to assess the impact of BM and PD-L1 status on outcomes in mUC patients treated with ICIs. PATIENTS AND METHODS: This post hoc analysis of the DANUBE study included 1032 mUC patients treated with durvalumab (D), D + tremelimumab (T), or standard chemotherapy (SoC). Patients were categorized by BM status and assessed for median overall survival (mOS) and median progression-free survival (mPFS) stratified by PD-L1 expression and treatment arm.  RESULTS: Among all patients enrolled in the study, those with BM had a lower mOS than those with no BM (8.7 vs. 15.8 months; P < .0001). Patients with BM and high PD-L1 expression, treated with D or D + T, had numerically longer mOS than patients with BM and low PD-L1 expression. In contrast, in the chemotherapy arm, there was no difference in mOS for BM or no BM, based on PD-L1 expression. Patients with BM had shorter mPFS compared to no BM (2.6 vs. 5.4 months; P < .0001). The study is limited by its post hoc nature. CONCLUSION: Presence of BM was associated with worse outcomes across treatment arms. Patients with BM and high PD-L1 expression treated with D or D + T had longer mOS, suggesting potential benefits of ICIs in this subgroup. Consideration of BM and PD-L1 status in treatment decisions for mUC patients receiving ICIs may improve clinical outcomes.

Analysis of risk factors for cancer-specific survival in neoadjuvant chemotherapy nonresponsive disease of muscle-invasive bladder cancer: A multicentre study from the Turkish Urooncology Association Bladder Tumor study group.

OBJECTIVE: To investigate the risk factors affecting cancer-specific survival (CSS) in nonresponsive disease to neoadjuvant chemotherapy (NAC) among patients with muscle-invasive bladder cancer (MIBC) who were treated with NAC and radical cystectomy (RC). METHODS: Patients with MIBC who underwent NAC and RC were retrospectively examined. By comparing clinical and pathological stages, patients whose pathological stage was lower than clinical stage were categorized as "NAC-responsive" and the remainder as "NAC-non-responsive." Apart from pathologic staging, variables compared between groups included age, gender, Eastern Cooperative Oncology Group (ECOG) score, clinical stages, NAC type and cycle number, durations between MIBC diagnosis and NAC initiation and RC, presence of hydronephrosis, number of lymph nodes removed, and variant histology of urothelial bladder cancer. CSS analysis was performed by construction of Kaplan-Meier survival curves and multivariable Cox regression was performed to identify the prognosticators in the NAC-non-responsive-group. RESULTS: Ninety-two patients were included with a mean age was 61.5 ± 8.5 years, of whom 84.8% were men. The NAC regimen used was predominantly gemcitabine-cisplatin (88%) and the median cycle number was 4. Fifty-six (60.9%) patients were NAC-non-responsive. There was a significantly lower proportion of patients receiving ≥4 cycles (46.4% vs. 66.7%) and a higher rate of patients with ECOG score ˃1 (33.9% vs. 11.1%) in the NAC-non-responsive-group compared to the NAC-responsive-group (both P < 0.05). Other variables were similar between groups. In multivariable analysis, only ypN+ was found to be an independent prognosticator for CSS in NAC-non-responsive-group (HR: 2.725, CI95%:1.017-7.303). CONCLUSION: Although higher ECOG scores and lower cycle numbers appears to be associated factors in NAC-non-responsive disease, only ypN(+) status was a prognosticator for CSS in this population.

Niraparib Enhances and Synergizes with Ganglioside GD2 to Potentiate its Inhibitory Effect on Bladder Cancer Cells.

PURPOSE: This study aimed to study the inhibitory effect of niraparib alone or in combination with GD2 specific antibody on Bladder Cancer (BCa). METHODS: The migration ability of BCa cells was assessed through a scratch assay. CCK-8 assay was performed to evaluate the viability of BCa cells, and Transwell invasion assays were utilized to examine invasive capacity. The expression levels of E-cadherin and vimentin in BCa cells were measured using QRT-PCR. RESULTS: Western blot showed the EMT level to be the lowest in the niraparib+GD2 group. The transwell invasion assay suggested that the invasion ability of BCa cells was weakened in the niraparib+ GD2 group. CCK8 assay indicated that the proliferation ability of BCa cells was decreased. Scratch test suggested that the migration ability of BCa cells was weakened. PCR result showed that the niraparib + GD2 group had the most significant inhibitory effect on mRNA expression of EMT markers. CONCLUSION: Niraparib combined with a GD2-specific antibody exerted a more prominent inhibitory effect on BCa.

Non-functional muscle-invasive bladder paraganglioma-a case report.

Background: Extra-adrenal pheochromocytoma (paraganglioma) of the urinary bladder is a rare tumor, accounting for 0.05% of bladder tumors and less than 1% of all paragangliomas. In the genitourinary tract, paragangliomas are most commonly found in the bladder. These tumors have aggressive malignant potential, so complete surgical resection for localized disease is important. Paragangliomas may be non-functional or functional with catecholamine secretions. Although these tumors are rare and difficult to distinguish from urothelial carcinoma (UC), intraoperative manipulation of these tumors may lead to a catecholamine surge and intraoperative complications. Preoperative or early intraoperative recognition of this tumor would facilitate appropriate alpha blockade to minimize morbidity. Case Description: Herein we report a rare non-functional paraganglioma arising from the bladder of a 46-year-old male. This case is notable for the location of the mass, requiring a 70-degree cystoscopic lens for complete visualization near the bladder neck, and for the identification of a golden-yellow sessile mass during the resection. Upon visualization of this mass, the operation should be paused for close hemodynamic monitoring and assess for signs of hypertensive crisis prior to continuing without alpha blockade. Conclusions: Suspected localized bladder paraganglioma cases should be optimized hemodynamically and managed surgically. Visualization of a sessile bladder mass on gross examination with golden-yellow tumor during the resection should prompt suspicion for a paraganglioma. Biochemical evaluation with serum or urine catecholamines, metanephrines, and normetanephrines should be performed to assess for tumor functionality.

News and prospects on radiotherapy for bladder cancer: Is trimodal therapy becoming the gold standard?

Trimodal therapy consisting of transurethral resection of bladder tumors followed by radiotherapy and chemotherapy, has emerged as a valuable therapeutic alternative to radical cystectomy in patients with muscle invasive bladder cancer. Concomitant radiosensitising chemotherapy is a component of trimodality increasing locoregional control compared to radiotherapy alone. The combinations 5-fluorouracil with mitomycin or cisplatin are the best supported in the literature. Gemcitabine appears to be a feasible and promising alternative. There is considerable international heterogeneity in terms of dose, volumes and fractionation. The most commonly used regimens are moderately hypofractionated (55Gy in 20 fractions over 4 weeks) and normofractionated (64Gy in 32 fractions) regimens. Radiotherapy for bladder cancer is an effective and evolving treatment, with current technical developments, and studies of new combinations with systemic treatments underway.

Analysis of the Application of the Micrometric Substaging System to Predict Recurrence and Progression in a Cohort of Patients with pT1 High-Grade Non-Muscle Invasive Bladder Cancer.

BACKGROUND: The World Health Organization (WHO) classification system for bladder cancer (BC) advocates for the substaging of pT1 disease, which may improve the prediction of cancer recurrence and progression. This study aims to evaluate the application and prognostic significance of a micrometric substaging system, utilising a 1 mm cut-off depth of invasion in patients with pT1 BC. METHODS: We retrospectively reviewed all patients diagnosed with pT1 High-Grade Non-Muscle Invasive Bladder Cancer (NMIBC) at our institution. Lamina propria infiltration was categorised using a 1 mm cut-off to differentiate between Focal (<1 mm) or Extended (≥1 mm) disease, dividing the patients into Focal and Extended groups. RESULTS: The study included 114 patients, with a median (Interquartile Range (IQR)) age of 78 (71-87) and a Charlson Comorbidity Index (CCI) of 6 (5-7). The median follow-up was 33 (20-53) months. Of these, 56 patients (49.0%) were classified as having focal invasive, while 58 (51.0%) had Extended invasion. Demographic and pathological characteristics were evenly distributed between the two groups without significant differences (p > 0.05). However, Extended disease was more prevalent at initial diagnosis (Odds Ratio (OR) 5.44, p = 0.003). Multivariate analysis identified a first diagnosis of BC, pathological Grade 3 (G3), presence of Carcinoma in situ (CIS) and residual tumour at second resection as independent predictors of Extended pT1. Recurrence rates, progression rates and cancer-specific mortality were 41.2%, 5.3% and 1.8%, respectively. There were no statistically significant differences between the Focal and Extended groups in 3-year recurrence-free (58.9% vs 63.8%, p = 0.654), progression-free (92.9% vs 96.5%, p = 0.270) and cancer-specific survival (100% vs 98.3%, p = 0.425) rates. CONCLUSIONS: In this retrospective, single-centre study, substaging by depth of invasion did not predict recurrence, progression or cancer-specific mortality in patients with pT1 NMIBC. The initial diagnosis of pT1 BC, presence of G3, CIS and residual tumour at the second resection were identified as independent predictors of Extended pT1.

Comprehensive Analysis of the Significance of Breast Cancer Gene 1 (BRCA-1) in Bladder Cancer.

Background: Bladder carcinoma (BLCA) is characterized by high morbidity, mortality, and treatment costs. Breast cancer gene 1 (BRCA1), a tumor suppressor gene, inhibits the development of malignant tumors. However, research on the significance of BRCA1 in BLCA is limited. This study aims to explore the importance of BRCA1 in BLCA using bioinformatic methods and immunohistochemistry. Methods: Gene expression, clinical, and survival data were collected from the TCGA databases through the UCSC Xena platform (http://xena.ucsc.edu/). The TPM data from the TCGA and GETEx databases were integrated using the GEPIA database (http://GEPIA.cancer-pku.cn). The study then explored the differential expression, survival prognosis, functional enrichment, and immune cell infiltration analyses of BRCA1 in BLCA. A PPI network of BRCA1 was constructed using the STRING database, and a BRCA1-associated gene-gene interaction network was generated using the GeneMANIA database. Immunohistochemistry (IHC) assays were performed to verify the expression levels of BRCA1 in bladder tumour tissues and adjacent normal tissues. Results: BRCA1 is associated with BLCA. Differential analysis indicated that BRCA1 acts as a risk factor for BLCA but does not show significant expression differences across genders, stages, tumor stages, lymph node stages, or metastasis stages. Additionally, staging was based on the eighth edition of the American Joint Committee on Cancer (AJCC) for BLCA. Co-expression network and Gene Set Enrichment Analysis (GESA) confirmed that BRCA1 is involved in various BLCA pathways. Furthermore, BRCA1 expression was also linked to immune cell infiltration. However, survival prognosis analysis revealed no significant correlation between the prognosis of BLCA and BRCA1. Conclusion: We demonstrated that BRCA1 is a prospective predicted and immunological biomarker in BLCA, offering new avenues for potential therapies.

Effect of extending the period from oral administration of 5-aminolevulinic acid hydrochloride to photodynamic diagnosis during transurethral resection for non-muscle invasive bladder cancer on diagnostic accuracy and safety: a single-arm multicenter phase III trial.

BACKGROUND: In Japan, the authorized period (2-4 h) between oral administration of 5-aminolevulinic acid hydrochloride (5-ALA) and transurethral resection for non-muscle invasive bladder cancer (NMIBC) may restrict photodynamic diagnosis (PDD) usage. Therefore, this prospective, single-arm, phase III study aimed to evaluate the diagnostic accuracy and safety of PDD at an extended administration period (4-8 h). METHODS: From January 2022 to May 2023, 161 patients with NMIBC were enrolled from eight hospitals. The primary endpoint was the blue light (BL) sensitivity of pathologically positive biopsies. The secondary endpoints were a comparison of the specificity and positive and negative prediction rates under BL and white light (WL) conditions. RESULTS: A total of 1242 specimens comprising 337 histological NMIBC specimens were analyzed. BL-sensitivity was 95.3%. Its lower limit of 95% confidence interval (92.4-97.3%) exceeded the threshold (70%) of non-inferiority to authorized usage. Sensitivity and specificity were significantly higher and lower for BL than those for WL (95.3% vs. 61.1%, P < 0.001; 52.7% vs. 95.2%, P < 0.001), respectively. The positive and negative predictive rates were significantly lower and higher for BL than those for WL (42.9% vs. 82.7%, P < 0.001; 96.8% vs. 86.8%, P < 0.001), respectively. Of the 145 patients receiving 5-ALA, 136 (93.8%) and 75 (51.7%) experienced 377 adverse events and 95 adverse reactions, respectively, most of which were grade 1 or 2. CONCLUSION: For extended period, the efficacy of PDD for NMIBC was similar to that of authorized period, in terms of higher sensitivity and lower specificity compared with WL, and the safety was acceptable.

Sonodynamic Therapy for Intestinal Obstruction Caused by Intestinal Metastasis of Bladder Cancer: A Case Report.

This paper presents a case report of a patient with intestinal obstruction caused by intestinal metastasis of bladder cancer treated with sonodynamic therapy. Sonodynamic therapy is a novel anti-tumor therapy that is safe, effi- cacious, and has minimal side effects. After treatment, the patient's intestinal obstruction was effectively relieved.

Strategies to Improve Clinical Outcomes and Patient Experience Undergoing Transurethral Resection of Bladder Tumor.

PURPOSE OF REVIEW: To describe patient experiences of transurethral resection of bladder tumor (TURBT) and review recent advances in enhancing clinical outcomes. RECENT FINDINGS: High rates of recurrence and progression of non-muscle invasive bladder tumors expose patients to multiple TURBT procedures throughout their disease process. Understanding the impact of TURBT on quality of life and patient experiences is crucial for shared decision-making, thus enhanced recovery protocol trials are being explored to improve patient outcomes. The variability in TURBT practices worldwide contributes to differing bladder tumor recurrence rates, prompting efforts to standardize practices by evaluating the impact of patient, hospital, and surgeon factors. For select cases, less intensive surveillance regimens have reduced toxicities and costs without compromising oncologic outcomes. New innovative approaches such as en bloc- and stratified resection techniques may reduce perioperative complications and improve clinical outcomes. Finally, neoadjuvant and ablative treatments have shown to be promising alternatives to TURBT, necessitating further investigation in this setting. TURBT is essential for diagnosing and treating bladder cancer. Reducing associated morbidities and improving surgical outcomes involve multifaceted approaches, including standardizing surgical practices, exploring innovative techniques, and optimizing surveillance regimens, all while promoting patient quality of life. Neoadjuvant therapies as alternative treatments are on the horizon and may ultimately change the landscape of bladder cancer care.

Identification of RNA-binding protein RBMS3 as a potential biomarker for immunotherapy in bladder cancer.

RNA-binding protein (RBP) plays pivotal roles in the malignant progression of cancer by regulating gene expression. In this paper, we aimed to develop RBP-based prognostic signature and identify critical hub RBPs in bladder cancer (BLCA). Firstly, a risk model based on differentially expressed RBP gens (DERBPs) between normal and tumor tissues was successfully established, which can predict the tumor stromal score and drug sensitivity. Then two another RBP risk models based on miRNA-correlated RBPs or lncRNA-correlated RBPs were also established, and RBMS3 was identified as the overlapping gene in the three models. Data from multiple bioinformatics databases revealed that RBMS3 was an independent prognostic factor for overall survival (OS), and was associated with an immunosuppressive tumor microenvironment (TME) in BLCA. Further, Single-cell RNA-Seq (scRNA-Seq) data and the human protein altas (HPA) database showed that RBMS3 expression (both mRNA and protein) were up-regulated in BLCA tumor and tumor stromal cells. Finally, RBMS3 was shown to be associated with worse response to BLCA immunotherapy. Overall, RBMS3 is a key prognostic RBP with TME remodeling function and may serve as a target for BLCA immunotherapy.

Multi-omics analysis unveils the predictive value of IGF2BP3/SPHK1 signaling in cancer stem cells for prognosis and immunotherapeutic response in muscle-invasive bladder cancer.

BACKGROUND: Muscle invasive bladder cancer (MIBC) is a life-threatening malignant tumor characterized by high metastasis rates, poor prognosis, and limited treatment options. Immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1 represent an emerging treatment for MIBC immunotherapy. However, the characteristics of patients likely to benefit from immunotherapy remain unclear. METHODS: We performed single-cell mass cytometry (CyTOF) analysis of 179,483 single cells to characterize potential immunotherapy-related cancer stem cells (CSCs)-like populations in the tumor microenvironment of 38 MIBC tissues. The upregulated expression of IGF2BP3 in CD274 + ALDH + CSC-like cells, which was associated with poor clinical prognosis, was analyzed by bulk RNA-sequencing data from an in-house cohort. The functional role of IGF2BP3 was determined through cell proliferation, colony formation, cell apoptosis and sphere formation assays. The regulation of SPHK1 expression by IGF2BP3 was  investigated using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and bulk RNA-sequencing (bulk RNA-seq). We further utilized single-nucleus RNA sequencing (snRNA-seq) data from 67,988 cells of 25 MIBC tissues and single-cell RNA sequencing (scRNA-seq) data from MIBC patient-derived organoids to characterize the molecular features of bladder cancer cells co-expressing IGF2BP3 and SPHK1. Spatial transcriptomics (ST) and co-detection by indexing (CODEX) analysis were used to describe the spatial distribution and interactions of IGF2BP3 + SPHK1 + bladder cancer cells and immune cells. RESULTS: A subset of CD274 + ALDH + CSC-like cells was identified, associating with immunosuppression and low survival rates in MIBC patients. IGF2BP3, an m6A reader gene, was found to be upregulated in the CD274 + ALDH + CSC-like cell population and linked to poor clinical prognosis in MIBC. Knockout of IGF2BP3 dramatically promoted cell apoptosis and reduced cell proliferation in T24 cells. By integrating MeRIP-seq and bulk RNA-seq analyses, we identified SPHK1 served as a substrate for IGF2BP3 in an m6A-dependent manner. Further snRNA-seq, scRNA-seq, ST, and CODEX analysis revealed a closer topographical distance between IGF2BP3 + SPHK1 + bladder cancer cells and exhausted CD8 + T cells, providing one explanation for the superior response to immunotherapy in IGF2BP3 + SPHK1 + bladder cancer cells-enriched patients. Finally, an ICI-associated signature was developed based on the enriched genes of IGF2BP3 + SPHK1 + bladder cancer cells, and its potential ability to predict the response to immunotherapy was validated in two independent immunotherapy cohort. CONCLUSIONS: Our study highlighted the critical involvement of the IGF2BP3/SPHK1 signaling in maintaining the stemness of CSCs and promoting MIBC progression. Additionally, these findings suggested that the IGF2BP3/SPHK1 signaling might serve as a biomarker for prognosis and immunotherapy response in MIBC.

Comparative analysis of amide proton transfer and diffusion-weighted imaging for assessing Ki-67, p53 and PD-L1 expression in bladder cancer.

RATIONALE AND OBJECTIVES: To evaluate amide proton transfer (APT) imaging for assessing Ki-67, p53 and PD-L1 status in bladder cancer (BC) and compare its diagnostic efficacy with that of diffusion-weighted imaging (DWI). MATERIALS AND METHODS: Consecutive patients suspected of BC were recruited for preoperative multiparametric MRI. APT signal was quantified by asymmetric magnetization transfer ratio (MTRasym). MTRasym and apparent diffusion coefficient (ADC) were measured by two radiologists, with interobserver agreement assessed. Spearman's correlation analyzed MTRasym values and molecular markers. The Whitney U test evaluated MTRasym and ADC variation based on molecular marker status. Optimal cutoff points were determined using area under the curve (AUC) analysis. RESULTS: 88 patients (72 ± 10 years; 77 men) with BC were studied. MTRasym values were significantly correlated with Ki-67, p53 and PD-L1 levels (P < 0.05). Higher MTRasym values were found in high Ki-67 expression BCs (1.89% [0.73%] vs. 1.23% ± 0.26%; P < 0.001), high p53 expression BCs (1.63% [0.56%] vs. 1.24% [0.56%]; P < 0.001) and positive PD-L1 expression BCs (2.02% [0.81%] vs. 1.48% [0.38%]; P < 0.001). Lower ADCs were found in high Ki-67 expression BCs (1.06 ×10-3 mm2/s [0.32 ×10-3 mm2/s] vs. 1.38 ×10-3 mm2/s [0.39 ×10-3 mm2/s]; P < 0.001). For p53 status, an MTRasym threshold of 1.27% had 95% sensitivity, 60% specificity, and AUC of 0.781. For PD-L1 status, a 1.90% threshold had 88% sensitivity, 92% specificity, and AUC of 0.859. CONCLUSION: APT may significantly enhance the preoperative assessment of BC aggressiveness and inform targeted immunotherapy decisions, with performance superior to DWI.

Immunohistochemical markers in predicting behavior of bladder urothelial carcinoma.

Background: Bladder cancer is the 5th most prevalent cancer among Iranian men. Finding prognostic markers to predict behavior of this cancer can help us to choose the best treatment for patients from the first place. We aimed to evaluate the correlation of immunohistochemical markers with tumor stage, grade and prognosis of disease. Methods: In this study, we reassessed the specs of proven UC among Iranian patients. Sixty specimens were collected, contained of 30 low grade and 30 high grade urothelial carcinomas. All slides were assessed by immunohistochemistry study for p21, p27, Her-2/neu, E-cadherin, and CD10. Data were analyzed by SPSS 18.0 and a p-value < 0.05 was considered significant. Results: We evaluated 60 patients in this study with mean age of 66±11 years and majority of them are men. High expression of p27 showed significant correlation with LGUC (P=0.030). HGUC related with high expression of Her-2/neu, CD10 and aberrant expression of E-Cadherin (P<0.0001). Aberrant E-Cadherin and high expression of CD10 are associated with higher tumor stage (P=0.000). CD10 intensity was the only immunohistochemical markers to predict prognosis (P=0.010). Conclusion: In the present study, CD10 intensity is the only marker that directly predicts the prognosis. The higher intensity leads to poor prognosis (recurrence or metastasis). More studies must be done in this aspect to resolve the controversies and clarify the role of immunohistochemical markers in predicting BC behaviors.