Diagnosis Of Bladder Cancer Research Articles

Recent Progress in Nanomaterial-Based Biosensors and Theranostic Nanomedicine for Bladder Cancer.

Bladder cancer (BCa) is one of the most expensive and common malignancies in the urinary system due to its high progression and recurrence rate. Although there are various methods, including cystoscopy, biopsy, and cytology, that have become the standard diagnosis methods for BCa, their intrinsic invasive and inaccurate properties need to be overcome. The novel urine cancer biomarkers are assisted by nanomaterials-based biosensors, such as field-effect transistors (FETs) with high sensitivity and specificity, which may provide solutions to these problems. In addition, nanomaterials can be applied for the advancement of next-generation optical imaging techniques and the contrast agents of conventional techniques; for example, magnetic resonance imaging (MRI) for the diagnosis of BCa. Regarding BCa therapy, nanocarriers, including mucoadhesive nanoparticles and other polymeric nanoparticles, successfully overcome the disadvantages of conventional intravesical instillation and improve the efficacy and safety of intravesical chemotherapy for BCa. Aside from chemotherapy, nanomedicine-based novel therapies, including photodynamic therapy (PDT), photothermal therapy (PTT), chemodynamic therapy (CDT), sonodynamic therapy (SDT), and combination therapy, have afforded us new ways to provide BC therapy and hope, which can be translated into the clinic. In addition, nanomotors and the nanomaterials-based solid tumor disassociation strategy provide new ideas for future research. Here, the advances in BCa diagnosis and therapy mentioned above are reviewed in this paper.

Flexible Point-of-Care Electrodes for Ultrasensitive Detection of Bladder Tumor-Relevant miRNA in Urine.

Portable point-of-care testing (POCT) is currently drawing enormous attention owing to its great potential for disease diagnosis and personal health management. Electrochemical biosensors, with the intrinsic advantages of cost-effectiveness, fast response, ease of miniaturization, and integration, are considered as one of the most promising candidates for POCT application. However, the clinical application of electrochemical biosensors-based POCT is hindered by the decreased detection sensitivity due to the low abundance of disease-relevant biomolecules in extremely complex biological samples. Herein, we construct a flexible electrochemical biosensor based on single-stranded DNA functionalized single-walled carbon nanotubes (ssDNA-SWNTs) for high sensitivity and stability detection of miRNA-21 in human urine to achieve bladder cancer (BCa) diagnosis and classification. The ssDNA-SWNT electrodes with a 2D interconnected network structure exhibit a high electrical conductivity, thus enabling the ultrasensitive detection of miRNA-21 with a detection limit of 3.0 fM. Additionally, the intrinsic flexibility of ssDNA-SWNT electrodes endows the biosensors with the capability to achieve high stability detection of miRNA-21 even under large bending deformations. In a cohort of 40 BCa patients at stages I-III and 44 negative control samples, the constructed ssDNA-SWNT biosensors could detect BCa with a 92.5% sensitivity, an 88.6% specificity, and classify the cancer stages with an overall accuracy of 81.0%. Additionally, the flexible ssDNA-SWNT biosensors could also be utilized for treatment efficiency assessment and cancer recurrence monitoring. Owing to their excellent sensitivity and stability, the designed flexible ssDNA-SWNT biosensors in this work propose a strategy to realize point-of-care detection of complex clinical samples to achieve personalized healthcare.

Designing Intelligent Nanomaterials to Achieve Highly Sensitive Diagnoses and Multimodality Therapy of Bladder Cancer.

Bladder cancer (BC) is among the most common malignant tumors of the genitourinary system worldwide. In recent years, the rate of BC incidence has increased, and the recurrence rate is high, resulting in poor quality of life for patients. Therefore, how to develop an effective method to achieve synchronous precise diagnoses and BC therapies is a difficult problem to solve clinically. Previous reports usually focus on the role of nanomaterials as drug delivery carriers, while a summary of the functional design and application of nanomaterials is lacking. Summarizing the application of functional nanomaterials in high-sensitivity diagnosis and multimodality therapy of BC is urgently needed. This review summarizes the application of nanotechnology in BC diagnosis, including the application of nanotechnology in the sensoring of BC biomarkers and their role in monitoring BC. In addition, conventional and combination therapies strategy in potential BC therapy are analyzed. Moreover, different kinds of nanomaterials in BC multimodal therapy according to pathological features of BC are also outlined. The goal of this review is to present an overview of the application of nanomaterials in the theranostics of BC to provide guidance for the application of functional nanomaterials to precisely diagnose and treat BC.

Is high accuracy of Vesical Imaging-Reporting and Data System (VI-RADS) sufficient for its implementation in the urological practice?

Currently, the only method used to differentiate between MIBC and NMIBC is transurethral resection of the bladder tumour (TURBT). Magnetic resonance and Vesical Imaging-Reporting and Data System (VI-RADS) would allow for discrimination between NMIBC and MIBC. We evaluate the sensitivity and specificity of VI-RADS in the diagnosis of muscle-invasive bladder cancer and discuss its value in everyday urological practice. 64 patients with bladder cancer (BC) were enrolled into this prospective study. Multiparametric magnetic resonance imaging (mpMRI) was performed before transurethral resection of the bladder tumour (TURBT) and evaluated using the VI-RADS score. Score were compared to histopathology results. We evaluated the sensitivity, specificity, positive and negative predictive value of this system using both cut-off VI-RADS ≥ 3 and ≥ 4. Sensitivity of 92.3% (95%CI: 64.0; 99.8), specificity of 81.4% (95%CI: 69.1; 90.3), positive predictive value of 52.2% (95%CI: 30.6; 73.2) and negative predictive value of 98.0% (95%CI: 89.1; 99.9) was determined using cut off VI-RADS ≥ 3, while sensitivity of 76.9% (95%CI: 46.2; 95.0), specificity of 91.5% (95%CI: 81.3; 97.2), positive predictive value of 66.7% (95%CI: 38.4; 88.2), and negative predictive value of 94.7% (95%CI: 85.4; 98.9) was determined using cut-off VI-RADS ≥ 4. Based on our results, we consider the optimal cut-off point to be VI-RADS ≥ 3 with the overall prediction accuracy of 83.3% (95%CI: 72.7; 91.1). We acknowledge that mpMRI provides valuable information with regard to BC staging, however, despite its high overall accuracy, we do not consider the VI-RADS could replace TURBT in discrimination between non-muscle invasive and MIBC.

Impact of Age at Diagnosis of Bladder Cancer on Survival: A Surveillance, Epidemiology, and End Results-Based Study 2004-2015.

An older age contributes to the development of bladder cancer. However, the relationship between advanced age at the diagnosis and prognosis of bladder cancer has been few reported. This study aimed to determine the effect of age on survival in bladder cancer with different subgroups. 117,275 patients with bladder cancer, identified from the Surveillance, Epidemiology, and End Results database during 2004-2015 in America, were divided into 4 age groups (≤54, 55 to 64, 65 to 74, and ≥75 years). Multivariable Cox proportional-hazards model and competing risk model were conducted according to different age groups. Heat maps were plotted to show the impact of age on survival in subgroups classified by other clinicopathological variables. Moreover, restricted cubic spline was used to model the association between age and the risk of death. Patients aged ≥75years had shorter overall survival in comparison with those aged ≤54years (hazard ratio [HR] = 5.36, 95% confidence interval [CI] = 5.13-5.59). Compared with patients aged ≤54years, patients older than 75years experienced a decreased rate of bladder cancer-specific survival (subdistribution HR = 2.15, 95% CI = 2.04-2.25). Heat maps also showed that older ages were associated with worse overall cumulative mortality and bladder cancer-specific cumulative mortality. Similarly, restricted cubic spline verified the impact of age on survival of bladder cancer. Age at diagnosis of bladder cancer was found to be a significant predictor for the worse overall survival and bladder cancer-specific survival even in an era with more effective therapies. Exploring the reasons why older age contributes to poor outcomes for bladder cancer will be the focus of future research.

Application of nanotechnology in bladder cancer diagnosis and therapeutic drug delivery.

Bladder cancer (BC) is one of the most common malignant tumors in the urinary system, and its high recurrence rate is a great economic burden to patients. Traditional diagnosis and treatment methods have the disadvantages of insufficient targeting, obvious side effects and low sensitivity, which seriously limit the accurate diagnosis and efficient treatment of BC. Due to their small size, easy surface modification, optical properties such as plasmon resonance, and surface enhanced Raman scattering, good electrical conductivity and photothermal conversion properties, nanomaterials have great potential application value in the realization of specific diagnosis and targeted therapy of BC. At present, the application of nanomaterials in the diagnosis and treatment of BC is attracting great attention and achieving rich research results. Therefore, this paper summarizes the recent research on nanomaterials in the diagnosis and treatment of BC, clarifies the existing advantages and disadvantages, and provides theoretical guidance for promoting the accurate diagnosis and efficient treatment of BC.

5α-reductase inhibitors and the risk of bladder cancer in a large, population-based cohort.

The ability of 5α-reductase inhibitors (5ARI) to reduce the risk of new onset bladder cancer (BC) has been studied with variable results. Our objective was to conduct a retrospective cohort population-based study to evaluate the association between 5ARI use, BC diagnosis, and BC mortality. We used routinely collected health care data from Ontario, Canada. Men ≥66 years of age with a prescription for a 5ARI were matched to non-5ARI users. Matching was done using a propensity score of selected covariates to make 96 different covariates comparable. We measured 5 additional baseline variables which may have impacted the risk of future BC diagnosis: prior cystoscopy, urine cytology, urinalysis, gross hematuria episodes, and transurethral resection of a bladder lesion. Only the first period of continuous usage of 5ARIs was considered. The prespecified at-risk period for outcomes started 1 year after initiating therapy and ended at the last date of 5ARI exposure + 1 year. We identified 93,197 men who initiated 5ARI therapy (52% dutasteride, and 48% finasteride) between 2003 and 2013 and matched them 1:1 to men who did not start a 5ARI. The median at-risk period for the 5ARI group was 1.68 years (interquartile range 1.00, 4.27). With adjustment for the variables related to prior BC investigations there was no significant difference in BC diagnosis (hazard ratio [HR] 1.05, 95% confidence interval [CI] 0.82-1.32) during the period of 0 to <2 years of 5ARI use; however, after ≥2 years of 5ARI use, the risk of BC diagnosis was significantly lower among the 5ARI group (HR 0.82, 95% CI 0.79-0.94). In a similarly adjusted model, BC mortality was lower among 5ARI users, but no longer statistically significant (HR 0.82, 95% CI 0.65, 1.02). When stratified by type of 5ARI, finasteride significantly reduced the risk of BC diagnosis after ≥2 years of continuous use (HR 0.86, 95% CI 0.76, 0.96); however, dutasteride did not (HR 0.92, 95% CI 0.83, 1.03). In a large cohort of men, the use of a 5ARI was associated with a significantly decreased the risk of BC diagnosis after more than 2 years of continuous therapy.

Expression of TMEFF2 gene and significance of initiation methylation in bladder cancer

Objective: To analyze the expression and significance of TMEFF2 gene methylation in bladder cancer. Methods: The promoter region methylation level of the MEFF 2 gene was analyzed by applying the expression database and gene methylation.64 urine samples were detected by demethylated drug-nitrogen-2 deoxycytidine to observe the changes of cell invasion and apoptotic valence, and its application value in bladder cancer was analyzed by applying high expression of TMEFF2 gene. Results: Drug treatment of bladder cancer cells showed that the appreciation and migration of bladder cancer were inhibited, but the number of apoptosis increased. Conclusion: TMEFF2 gene promoter methylation is one of the markers of bladder cancer and plays an important role in the diagnosis of bladder cancer.

Loneliness, spiritual well-being, and death perception, as well as their risk factors in urological cancer patients.

Cancer patients commonly suffer from loneliness, poor spiritual status, and fear of death; however, these evaluations are rarely revealed in urological cancer patients. Thus, this study aimed to assess the loneliness, spiritual well-being, and death perception, as well as their risk factors in urological cancer patients. A total of 324 urological (including renal, bladder, and prostate) cancer patients and 100 healthy controls were included. The University of California and Los Angeles loneliness scale (UCLA-LS), functional assessment of chronic illness therapy-spiritual well-being (FACIT-Sp), and death attitude profile-revised (DAP-R) scores were evaluated. The results showed that the UCLA-LS score was higher, but the FACIT-Sp score was lower in urological cancer patients than in healthy controls. According to the DAP-R score, fear of death, death avoidance, and approaching death acceptance were elevated, but neutral acceptance was lower in urological cancer patients than in healthy controls. Among urological cancer patients, the UCLA-LS score was highest but the FACIT-Sp score was lowest in bladder cancer patients; regarding the DAP-R score, fear of death and death avoidance were highest, but approaching death acceptance was lowest in bladder cancer patients. Interestingly, single/divorced/widowed status, bladder cancer diagnosis, higher pathological grade, surgery, systemic treatment, and local treatment were independent factors for higher UCLA-LS score or lower FACIT-Sp score. In conclusion, urological cancer (especially bladder cancer) patients bear increased loneliness and reduced spiritual well-being; they also carry higher fear of death, death avoidance, and approaching death acceptance but lower neutral acceptance of death.

Radiomics vs radiologist in bladder and renal cancer. Results from a systematic review.

Radiomics in uro-oncology is a rapidly evolving science proving to be a novel approach for optimizing the analysis of massive data from medical images to provide auxiliary guidance in clinical issues. This scoping review aimed to identify key aspects wherein radiomics can potentially improve the accuracy of diagnosis, staging, and grading of renal and bladder cancer. A literature search was performed in June 2022 using PubMed, Embase, and Cochrane Central Controlled Register of Trials. Studies were included if radiomics were compared with radiological reports only. Twenty-two papers were included, 4 were pertinent to bladder cancer, and 18 to renal cancer. Radiomics outperforms the visual assessment by radiologists in contrast-enhanced computed tomography (CECT) to predict muscle invasion but are equivalent to CT reporting by radiologists in predicting lymph node metastasis. Magnetic resonance imaging (MRI) radiomics outperforms radiological reporting for lymph node metastasis. Radiomics perform better than radiologists reporting the probability of renal cell carcinoma, improving interreader concordance and performance. Radiomics also helps to determine differences in types of renal pathology and between malignant lesions from their benign counterparts. Radiomics can be helpful to establish a model for differentiating low-grade from high-grade clear cell renal cancer with high accuracy just from contrast-enhanced CT scans. Our review shows that radiomic models outperform individual reports by radiologists by their ability to incorporate many more complex radiological features.

Prognosis Prediction of Disulfidptosis-Related Genes in Bladder Cancer and a Comprehensive Analysis of Immunotherapy.

As a newly discovered mechanism of cell death, disulfidptosis is expected to help diagnose and treat bladder cancer patients. First, data obtained from public databases were analyzed using bioinformatics techniques. SVA packages were used to combine data from different databases to remove batch effects. Then, the differential analysis and COX regression analysis of ten disulfidptosis-related genes identified four prognostically relevant differentially expressed genes which were subjected to Lasso regression for further screening to obtain model-related genes and output model formulas. The predictive power of the prognostic model was verified and the immunohistochemistry of model-related genes was verified in the HPA database. Pathway enrichment analysis was performed to identify the mechanism of bladder cancer development and progression. The tumor microenvironment and immune cell infiltration of bladder cancer patients with different risk scores were analyzed to personalize treatment. Then, information from the IMvigor210 database was used to predict the responsiveness of different risk patients to immunotherapy. The oncoPredict package was used to predict the sensitivity of patients at different risk to chemotherapy drugs, and its results have some reference value for guiding clinical use. After confirming that our model could reliably predict the prognosis of bladder cancer patients, the risk scores were combined with clinical information to create a nomogram to accurately calculate the patient survival rate. A prognostic model containing three disulfidptosis-related genes (NDUFA11, RPN1, SLC3A2) was constructed. The functional enrichment analysis and immune-related analysis indicated patients in the high-risk group were candidates for immunotherapy. The results of drug susceptibility analysis can guide more accurate treatment for bladder cancer patients and the nomogram can accurately predict patient survival. NDUFA11, RPN1, and SLC3A2 are potential novel biomarkers for the diagnosis and treatment of bladder cancer. The comprehensive analysis of tumor immune profiles indicated that patients in the high-risk group are expected to benefit from immunotherapy.

Urine micro-RNA signature as a potential non-invasive diagnostic biomarker in bladder cancer.

Background: Bladder cancer (BC) is one of the most prevalent malignancies worldwide, 70% of patients initially diagnosed with superficial BC. In addition, 20% of BC patients with recurrence experience disease progression. Thus, identification of novel biomarkers for diagnosis, prognosis and therapeutic targets of BC will help to advance clinical diagnosis and treatment of this disease. MicroRNAs (miRNAs) are single stranded, non coding RNAs that are hypothesized to regulate gene expression at the post transcriptional level. This study aimed to assess the urine and tissue expression levels of miR-200, miR-145 and miR-21 in BC patients o evaluate their potential as noninvasive biomarkers. Subjects and methods: Urine and their corresponding tissue samples were collected from 111 BC patients and from 25 healthy controls. A quantitative real-time polymerase chain reaction method based on a TaqMan probe was used to evaluate the expression levels of miR‑200, miR‑145 and miR-21, the correlations between these miRNA expression levels in urine and tissues and certain clinicopathological parameters were investigated. Results: The expression of the 3 studied miRNAs was significantly higher in urine of low and high tumor grade BC patients compared to the controls and the expression were increased in BC tissues compared with those in normal bladder tissues, the results proved that the 3 miRNAs function as oncogenes. A marked positive correlation was observed between the mRNA expression of miR-200 and miR 21, with a coefficient of 0.511 and P value of 0.02. Conclusion: The results of the present study indicated that miR-200, miR-145 and miR-21 may function as oncogenes and have a potential to serve as an early noninvasive diagnostic biomarkers and therapeutic targets for treatment of BC.

Bladder and Kidney Cancer Diagnosis and Survival Increase With Medicare Eligibility at Age 65

Medicare eligibility at 65 has been associated with increased diagnosis and survival for certain cancers due to greater health care utilization. We aim to assess for a similar "Medicare effect" for bladder and kidney cancers, which has not been previously established. Patients diagnosed with bladder or kidney cancer from 2000-2018 at ages 60-69 years were identified with the Surveillance, Epidemiology, and End Results database. We used age-over-age percent change calculations to characterize trends in cancer diagnoses focusing on patients aged 65. Multivariable Cox models were used to compare cancer-specific mortality across ages at diagnosis. We identified 63,960 patients diagnosed with bladder cancer and 52,316 diagnosed with kidney cancer. Age-over-age change in diagnosis was highest for patients aged 65 compared to all other ages for both cancers (P < .01 for both). Stratified by stage, patients aged 65 had a higher age-over-age change than those aged 61-64 or 66-69 for in situ (P = .01, P < .01, respectively), localized (P = .03, P = .01), and regional (P = .02, P = .02) bladder cancer and localized (P = .01, P = .01) kidney cancer. Bladder cancer patients aged 65 had lower cancer-specific mortality than patients aged 66 (HR = 1.17, P = .01) and 69 (HR = 1.18, P = .01), while kidney cancer patients aged 65 had lower mortality than patients aged 64 (HR = 1.18, P < .01) and 66-69. The age of 65, marking the onset of Medicare eligibility, is associated with more diagnoses of bladder and kidney cancer. Patients diagnosed at age 65 demonstrate decreased bladder and kidney cancer-specific mortality.

Retracted: Computed Tomography Image Features under Deep Learning Algorithm Applied in Staging Diagnosis of Bladder Cancer and Detection on Ceramide Glycosylation.

[This retracts the article DOI: 10.1155/2022/7979523.].

Retracted: Multi-Slice Spiral Computed Tomography Image Features under Hybrid Iterative Reconstruction Algorithm in Staging Diagnosis of Bladder Cancer.

[This retracts the article DOI: 10.1155/2021/7733654.].

Abstract P032: A novel multiplex immunoassay for the early detection of bladder cancer

Abstract Background: We have identified a bladder cancer-associated signature which has been confirmed in several large cohorts, specifically noting its ability to identify smaller tumors (~1cm), which had an elevation at the time of diagnosis in one or more of the 10 biomarkers but not to the same extent as we see in the studies with primary de novo tumors (~3 cm). Thus, we have reported, as the tumor grows, as the grade increases and as the stage increases, there is a corresponding increase in the absolute levels of one or more of the biomarkers that comprise the bladder cancer-associated signature. Currently, the bladder cancer-associated signature is being tested in 4 large prospective studies; i) bladder cancer detection in subjects with gross hematuria, ii) bladder cancer detection in subjects with microscopic hematuria, iii) tumor surveillance in patients with a history of bladder cancer and iv) predicting response to intravesical BCG. In the tumor surveillance study, subjects are followed for 2 years to monitor for tumor recurrence. After enrolling 300 subjects into this study as of May 2020, to date, we have noted tumors recurrences in the 21-24 months follow-up period in 20 subjects. This group was picked to generate the current preliminary data because they would have had several serial urine samples available for analysis. Interestingly of these 20 subjects (57 voided urine samples), the multiplex immunoassay noted an elevation of our bladder cancer-associated signature as early as 18 months prior to the clinical diagnosis of bladder cancer and an actual positive immunoassay in all 20 subjects at 12 months prior to the clinical diagnosis of bladder cancer. Trial Design: This is a single arm pilot study evaluating the feasibility of conducting a longitudinal study monitoring a high-risk population for the development of bladder cancer. Note–This pilot study is design to determine feasibility of recruiting, retaining, and testing a very high-risk cohort in hopes of noting a positive signal from our test. The subsequent definitive study would be expanded to include woman &amp;gt;50 years of age. Eligibility Criteria: Participants must be age 50 years or older, males, &amp;gt;30 pack year history of tobacco exposure, free of any malignancy, willing and able to give written informed consent, willing to provide voided urine sample, and able and willing to complete annual research clinic visits for 4 years. Trial Objectives: 1) To assess the ability to recruit and retain an appropriate high-risk group of subjects into a 4-year longitudinal study monitoring them for the development of bladder cancer. 2) To report the sensitivity and specificity of the multiplex immunoassay ability to detect bladder cancer in patients with high risk of developing bladder cancer: males, &amp;gt;50 years and &amp;gt;30 pack year history of tobacco exposure. 3) To develop a prediction risk calculator from this cohort using cutting edge machine learning techniques (e.g., random forest) incorporating biomarker data and clinical data. Accrual: The target enrollment is approximately 150 patients. Citation Format: Hideki Furuya, Charles J. Rosser. A novel multiplex immunoassay for the early detection of bladder cancer. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P032.

Optimized Decision Tree and Black Box Learners for Revealing Genetic Causes of Bladder Cancer

The number of studies in the literature that diagnose cancer with machine learning using genome data is quite limited. These studies focus on the prediction performance, and the extraction of genomic factors that cause disease is often overlooked. However, finding underlying genetic causes is very important in terms of early diagnosis, development of diagnostic kits, preventive medicine, etc. The motivation of our study was to diagnose bladder cancer (BCa) based on genetic data and to reveal underlying genetic factors by using machine-learning models. In addition, conducting hyper-parameter optimization to get the best performance from different models, which is overlooked in most studies, was another objective of the study. Within the framework of these motivations, C4.5, random forest (RF), artificial neural networks (ANN), and deep learning (DL) were used. In this way, the diagnostic performance of decision tree (DT)-based models and black box models on BCa was also compared. The most successful model, DL, yielded an area under the curve (AUC) of 0.985 and a mean square error (MSE) of 0.069. For each model, hyper-parameters were optimized by an evolutionary algorithm. On average, hyper-parameter optimization increased MSE, root mean square error (RMSE), LogLoss, and AUC by 30%, 17.5%, 13%, and 6.75%, respectively. The features causing BCa were extracted. For this purpose, entropy and Gini coefficients were used for DT-based methods, and the Gedeon variable importance was used for black box methods. The single nucleotide polymorphisms (SNPs) rs197412, rs2275928, rs12479919, rs798766 and rs2275928, whose BCa relations were proven in the literature, were found to be closely related to BCa. In addition, rs1994624 and rs2241766 susceptibility loci were proposed to be examined in future studies.

LncRNA UCA1 Participates in De Novo Synthesis of Guanine Nucleotides in Bladder Cancer by Recruiting TWIST1 to Increase IMPDH1/2.

Metabolic dysregulation has been identified as one of the hallmarks of cancer biology. Based on metabolic heterogeneity between bladder cancer tissues and adjacent tissues, we discovered several potential driving factors for the bladder cancer occurrence and development. Metabolic genomics showed purine metabolism pathway was mainly accumulated in bladder cancer. Long noncoding RNA urothelial carcinoma-associated 1 (LncRNA UCA1) is a potential tumor biomarker for bladder cancer diagnosis and prognosis, and it increases bladder cancer cell proliferation, migration, and invasion via the glycolysis pathway. However, whether UCA1 plays a role in purine metabolism in bladder cancer is unknown. Our findings showed that UCA1 could increase the transcription activity of guanine nucleotide de novo synthesis rate limiting enzyme inosine monophosphate dehydrogenase 1 (IMPDH1) and inosine monophosphate dehydrogenase 2 (IMPDH2), triggering in guanine nucleotide metabolic reprogramming. This process was achieved by UCA1 recruiting the transcription factor TWIST1 which binds to the IMPDH1and IMPDH2 promoter region. Increased guanine nucleotide synthesis pathway products stimulate RNA polymerase-dependent production of pre-ribosomal RNA and GTPase activity in bladder cancer cells, hence increasing bladder cancer cell proliferation, migration, and invasion. We have demonstrated that UCA1 regulates IMPDH1/2-mediated guanine nucleotide production via TWIST1, providing additional evidence of metabolic reprogramming.

Lysine N-methyltransferase SETD7 promotes bladder cancer progression and immune escape via STAT3/PD-L1 cascade.

Background: The immunotherapy sensitivity of patients with bladder cancer (BCa) remains low. As the role of protein methylation in tumorigenesis and development becomes clearer, the role of lysine N-methyltransferase SET domain containing 7 (SETD7) in the progression and immune escape of BCa is worth studying. Methods: The correlation between lysine methyltransferase family and prognosis or immunotheray sensitivity of BCa patients were analyzed, and SETD7 was screened out because of the significant correlation between its expression and survival data or immunotherapy sensitivity. The expression of SETD7 in BCa tissues and cell lines were explored. The functions of SETD7 were investigated by proliferation and migration assays. The role of SETD7 in BCa immune escape was validated by analyzing the correlation between SETD7 expression and tumor microenvironment (TME)-related indicators. The results were further confirmed by conducting BCa cell-CD8+ T cell co-culture assays and tumorigenesis experiment in human immune reconstitution NOG mice (HuNOG mice). Bioinformatic prediction, CO-IP, qRT-PCR, and western blot were used to validate the SETD7/STAT3/PD-L1 cascade. Results: SETD7 was highly expressed in BCa, and it was positively associated with high histological grade and worse prognosis. SETD7 promoted the proliferation and migration of BCa cells. The results of bioinformatics, in vitro co-culture, and in vivo tumorigenesis assays showed that SETD7 could inhibit the chemotoxis and cytotoxicity of CD8+ T cells in BCa TME. Mechanistically, bioinformatics analysis, CO-IP assay, qRT-PCR, and western blot results indicated that SETD7 could increase the expression of PD-L1 via binding and promoting STAT3. Conclusions: Taken together, SETD7 indicated poor prognosis and promoted the progression and immune escape of BCa cells. It has great potential to act as a new indicator for BCa diagnosis and treatment, especially immunotherapy.

Comprehensive optimization of urinary exfoliated tumor cells tests in bladder cancer with a promising microfluidic platform.

Enrichment of urinary exfoliated tumor cells (UETCs) is a noninvasive way of bladder cancer diagnosis, but the lack of specific capture and identification of tumor cells from the urine remains a limitation that impedes the development of liquid biopsy. The CytoBot® 2000, a novel circulating cell isolation and enrichment platform, was used for UETCs isolation after comprehensive optimization. The commercial cell lines of bladder cancer were used in spiking assay for cell recovery test. The flow cytometry and immunofluorescent staining assays were performed for expression validation of capture target and identification markers. The performance of optimized platform was validated by 159 clinical samples and analyzed using receiver operator characteristic curve. The chip that had a pore diameter of 15*20 μm could reduce the background residues while maintaining a higher cell recovery rate. We found that the cell capture ability of chip significantly improved after anti-EpCam antibody encapsulation, but not with T4L6FM1. In identification system optimization, the spiking assay and validation of clinical sample showed that the performance of CK20 and DBC-1 were better that pan-CK in tumor cell identification, in addition, the staining quality is more legible with CK20. The optimized capture chip is more specific for UETCs isolation. CK20 and DBC-1 are both sensitive biomarkers of UETCs in bladder cancer diagnosis. The performance of this optimized platform is excellent in clinical test that improves the accuracy of urine cell testing and provides a new alternative for the clinical application of BLCA liquid biopsy assessment.