Development Of Bladder Cancer Research Articles

SLC7A5 correlated with malignancies and immunotherapy response in bladder cancer

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

Exploring the DNA Methylation Profile of Genes Associated with Bladder Cancer in Bladder Tissue of Patients with Neurogenic Lower Urinary Tract Dysfunction

DNA methylation is an epigenetic process that commonly occurs in genes’ promoters and results in the transcriptional silencing of genes. DNA methylation is a frequent event in bladder cancer, participating in tumor initiation and progression. Bladder cancer is a major health issue in patients suffering from neurogenic lower urinary tract dysfunction (NLUTD), although the pathogenetic mechanisms of the disease remain unclear. In this population, bladder cancer is characterized by aggressive histopathology, advanced stage during diagnosis, and high mortality rates. To assess the DNA methylation profiles of five genes’ promoters previously known to be associated with bladder cancer in bladder tissue of NLUTD patients, we conducted a prospective study recruiting NLUTD patients from the neuro-urology unit of a public teaching hospital. Cystoscopy combined with biopsy for bladder cancer screening was performed in all patients following written informed consent being obtained. Quantitative methylation-specific PCR was used to determine the methylation status of RASSF1, RARβ, DAPK, hTERT, and APC genes’ promoters in bladder tissue samples. Twenty-four patients suffering from mixed NLUTD etiology for a median duration of 10 (IQR: 12) years were recruited in this study. DNA hypermethylation was detected in at least one gene of the panel in all tissue samples. RAR-β was hypermethylated in 91.7% samples, RASSF and DAPK were hypermethylated in 83.3% samples, APC 37.5% samples, and TERT in none of the tissue samples. In 45.8% of the samples, three genes of the panel were hypermethylated, in 29.2% four genes were hypermethylated, and in 16.7% and in 8.3% of the samples, two and one gene were hypermethylated, respectively. The number of hypermethylated genes of the panel was significantly associated with recurrent UTIs (p = 0.0048). No other significant association was found between DNA hypermethylation or the number of hypermethylated genes and the clinical characteristics of the patients. Histopathological findings were normal in 8.3% of patients, while chronic inflammation was found in 83.3% of patients and squamous cell metaplasia in 16.7% of patients. In this study, we observed high rates of DNA hypermethylation of genes associated with bladder cancer in NLUTD patients, suggesting an epigenetic field effect and possible risk of bladder cancer development. Recurrent UTIs seem to be associated with increased DNA hypermethylation. Further research is needed to evaluate the impact of recurrent UTIs and chronic inflammation in DNA hypermethylation and bladder cancer etiopathogenesis in NLUTD patients.

Abstract PR001: TRIM29 is required for basal bladder cancer invasive progression

Abstract TRIM29 (Tripartite Motif 29) also known ATDC, is an E3 ubiquitin ligase frequently upregulated in muscle-invasive bladder cancer (MIBC). We have previously shown TRIM29 global overexpression in a genetically engineered mouse model (GEMM) is sufficient to ` bladder cancer development and progression to MIBC. Other studies strongly suggest cytokeratin-5/14 (Krt5+/Krt14+) expressing basal-stem progenitor cells in the urothelium are the cells of origin for MIBC in mice. We therefore hypothesized that Trim29 expression in Krt5+ basal urothelial cells is required for development of MIBC in mice. To test this, we generated a GEMM harboring a Trim29 conditional KO allele and tamoxifen responsive Cre under control of the bovine Krt5promoter. Exposure of Krt5-CreERT2 Trim29flox/flox mice to tamoxifen resulted in activation of Cre and loss of Trim29 expression only in the Krt5+ basal urothelium. To induce bladder tumorigenesis, we utilized the urothelial specific carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in drinking water at 0.05%. After 6 months, tumor invasion was staged by a genitourinary pathologist based on depth of invasion: T1 (stromal invasive), T2 (muscle invasive) and T3 (deep muscle/peri-vesicular invasion). In agreement with previous studies, BBN exposure resulted in loss of Krt5-negative intermediate and superficial cells, and expansion of Krt5+/Krt14+ basal cells across the urothelium. In combination with a tamoxifen treatment this led to total Trim29 KO in the urothelium. All male Trim29 WT mice exposed to BBN developed Trim29+ bladder tumors, >50% of which demonstrated extensive progression to muscle-invasion (57% n=23). In contrast, only 16% of mice with Trim29 loss in Krt5+ basal cells developed MIBC (n=18). As an E3 ubiquitin ligase TRIM29 is known to target immune adaptor molecules, notably the stimulator of interferon genes (STING), for proteasomal degradation. We hypothesized TRIM29 targets STING during invasive progression and supports the establishment of an immune-privileged niche at the bladder cancer invasive front. We find TRIM29 expression in human bladder tissues is upregulated in the urothelium under stress and in MIBC tumors. In mice, BBN exposure upregulated Trim29 expression in the bladder urothelium which correlated with low urothelial Sting. In contrast, Krt5+ Trim29 loss resulted in significantly elevated Sting in the bladder urothelium. Multiplex immunofluorescence imaging and immunotyping of Trim29 KO mouse tissues revealed peritumoral enrichment of CD4+ and CD8+ T cells, CD206+ immunosuppressive macrophages, and CD4+FoxP3+ regulatory T cells. Taken together, these results suggest that TRIM29-mediated downregulation of STING in the bladder urothelium results in decreased immune surveillance at the tumor-stromal interface which expedites invasion and tumor burden. Citation Format: Alan Kelleher, Luke Broses, Yin Wang, Marian Henderson, Mark Day, Aaron Udager, Phillip Palmbos. TRIM29 is required for basal bladder cancer invasive progression [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr PR001.

Phytosanitary products from agriculture associated with the development of bladder cancer among farm owners and farm workers: a systematic review

Phytosanitary products from agriculture associated with the development of bladder cancer among farm owners and farm workers: a systematic review

Bladder Cancer Survivors Who Do Not Smoke Have Better Longitudinal Health Related Quality of Life Measures: An Assessment of the Comparative Effectiveness of Survivorship Health in Bladder Cancer (CEASE-BC) Study.

Cigarette smoking is the most common risk factor for the development of bladder cancer (BC), yet there is a paucity of data characterizing the relationship between smoking status and longitudinal Health Related Quality of Life (HRQoL) outcomes in patients with BC. We examined the association between smoking status and HRQoL among patients with BC. Data was sourced from a prospective, longitudinal study open between 2014 and 2017, which examined HRQoL in patients aged ≥ 18 years diagnosed with BC across North Carolina. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core instrument (QLQ-C30) was administered at 3, 12, and 24 months after BC diagnosis. Our primary exposure of interest was current smoking status. Linear regression using Generalized Estimating Equations was used to analyze the relationship between smoking status and various domains of the QLQ-C30. A total of 154 patients enrolled in the study. Eighteen percent were classified as smoking at 3 months from diagnosis, packs per day (PPD) ranged from < 0.5 to 2. When controlling for time from diagnosis, demographic covariates, cancer stage, and treatment type, mean differences (MD) for physical function (7.4), emotional function (5.6), and fatigue measures (-8.2) were significantly better for patients with BC who did not smoke. Patients with BC who do not smoke have significantly better HRQoL scores in the domains of physical function, emotional function, and fatigue. These results underscore the need to treat smoking as an essential component of BC care.

Abstract 1278: Differential urinary microbiome and its metabolic footprint in bladder cancer patients following BCG treatment

Abstract Introduction &amp; Objectives: Recent insights reveal a urinary microbiome, challenging prior beliefs about urine's sterility. Using 16S rRNA gene sequencing, a pivotal tool in mapping this microbiome, our study delves into the interplay between bladder cancer (BCa), BCG therapy, and the urinary microbiome. We analyzed bacterial profiles in benign and malignant samples, considering various clinical parameters. Materials &amp; Methods: A total of 88 patients participated in the study, comprising 30 individuals with benign diseases and 58 BCa patients. Urine samples were collected from patients with benign conditions and from BCa patients before and after BCG treatment. Malignant samples obtained before the completion of the intravesical BCG induction cycle were labeled 'Pre-BCG', while those collected after this cycle were termed 'Post-BCG'. Following collection, DNA was extracted and underwent 16S rRNA gene sequencing. The sequencing data was then utilized for bioinformatic analyses, which included metagenomic profiling and metabolic pathway inference. Results: Significant differences in bacterial compositions were observed between benign and malignant samples, with a metabolic signature suggesting toluene degradation pathway may mitigate bladder cancer development. In the post-BCG samples, we inferred elevations of 2-oxoglutarate, a BCG derivative, and L-methionine, which is associated with therapeutic benefits, compared to their pre-BCG counterparts. Furthermore, post-BCG samples showed microbial differences in responders and increased quinolone synthesis compared to non-responders. This is of significance due to quinolone's role in modulating DNA topoisomerase and mitochondrial functions, both pivotal in bladder cancer progression. Conclusions: Utilizing 16S rRNA gene sequencing, we drew comparisons between the urinary microbiomes of benign and malignant samples and suggested a potential pathway for bladder cancer occurrence. Following intravesical BCG treatment, certain microbial metabolic pathways seemed to offer therapeutic benefits to responders. Our study provides insights into the microbial influences on bladder cancer development and the varying responses to BCG treatment. Citation Format: Xuan-Mei Piao, Kyungchan Min, Young Joon Byun, Chuang-Ming Zheng, Seon-Kyu Kim, Seong-Hwan Park, Sungmin Moon, Kyeong Kim, Ho Won Kang, Won Tae Kim, Seok Joong Yun, Hansoo Park. Differential urinary microbiome and its metabolic footprint in bladder cancer patients following BCG treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1278.

Abstract 2199: Low-carbohydrate diet score and risk of bladder cancer: Findings from the Singapore Chinese Health Study

Abstract Background. Bladder cancer is a leading tumor of urinary tract with annually 570,000+ new cases and 200,000+ deaths worldwide. In the United States, the current incidence rate of bladder cancer is 15.8 per 100,000 population with more than 82,000 new cases and more than 16,000 deaths each year. Although smoking is established as a major risk factor for bladder cancer development, accounting for 30-50% cases, the role of other modifiable risk factors, including dietary in bladder cancer remains unclear. Low-carbohydrate diet (LCD) is a dietary pattern to restrict carbohydrate and to favor protein and/or fat intakes that has recently been well-accepted for weight loss. While its short-term effect to support the weight loss has been popular, its long-term effect on chronic diseases, including cancer, needs to be elucidated. In the current analysis, we sought to determine the association between LCD scores and bladder cancer risk in the Singapore Chinese Health Study (SCHS), an ongoing prospective cohort study consisting of more than 63,000 Chinese Singaporeans, 45- 74 years of age at baseline enrollment period 1995-1998. Methods. Total, animal-based and plant-based LCD scores were derived from the baseline dietary survey data, representing summed intake of carbohydrates, fats and proteins from all dietary, animal- and plant-food sources, respectively. Bladder cancer cases were ascertained using cancer registry. Cox proportional hazard regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for different LCD score levels with risk of bladder cancer. Results. By December 31, 2015, or after 17.6 years of follow-up, 250 bladder cancer cases were developed within the SCHS. Total LCD score was marginally associated with increased risk of bladder cancer (HRQ4vs.Q1=1.43, 95% CI: 0.98-2.09, Ptrend = 0.06). Animal-based LCD score was significantly associated with risk of bladder cancer. The HRs and respective 95% CIs of bladder cancer for quartiles 2, 3, and 4, compared with the lowest quartile, were 1.09 (0.76-1.56), 1.17 (0.81-1.70), and 1.53 (1.09-2.17) (Ptrend=0.01). The positive association was only present in men, ever smokers, never drinkers and individuals without history of type 2 diabetes (All P’sheterogeneity&amp;gt;0.05). Conclusions. In a prospective cohort study of more than 63,000 Chinese Singaporeans, we found that animal-based LCD score, representing a diet with lower carbohydrate and higher animal fat and protein, was significantly associated with increased risk of bladder cancer. Dietary modification is therefore suggested as an effective strategy for primary prevention of bladder cancer. Citation Format: Yen Thi-Hai Pham, Renwei Wang, Aizhen Jin, Woon-Puay Koh, Jian-Min Yuan, Hung N. Luu. Low-carbohydrate diet score and risk of bladder cancer: Findings from the Singapore Chinese Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2199.

Association of interleukin-17A and chemokine/vascular endothelial growth factor-induced angiogenesis in newly diagnosed patients with bladder cancer

BackgroundThe human interleukin-17 (IL-17) family comprises IL-17A to IL-17 F; their receptors are IL-17RA to IL-17RE. Evidence revealed that these cytokines can have a tumor-supportive or anti-tumor impact on human malignancies. The purpose of this study was to assess the expression of CXCR2, IL-17RA, and IL-17RC genes at the mRNA level as well as tissue and serum levels of IL-17A, vascular endothelial growth factor (VEGF), and transforming growth factor β (TGF-β) in patients with bladder cancer (BC) compared to control.ResultsThis study showed that gene expression of IL-17RA, IL-17RC, and CXCR2 in the tumoral tissue of BC patients was significantly upregulated compared with normal tissue. The findings disclosed a significant difference in the serum and tissue concentrations of IL-17A, VEGF, and TGF-β between the patient and the control groups, as well as tumor and normal tissues.ConclusionThis study reveals notable dysregulation of CXCR2, IL-17RA, and IL-17RC genes, alongside changes in IL-17A, VEGF, and TGF-β levels in patients with BC than in controls. These findings indicate their possible involvement in BC development and their potential as diagnostic and therapeutic targets.

Retracted: lncRNA MIR4435-2HG Accelerates the Development of Bladder Cancer through Enhancing IQGAP3 and CDCA5 Expression.

[This retracts the article DOI: 10.1155/2022/3858249.].

Mendelian randomization analysis reveals a protective association between genetically predicted systemic lupus erythematosus and renal cell carcinoma.

Observational studies have suggested that there may be a connection between systemic lupus erythematosus (SLE) and a higher likelihood of developing urological cancers, although the exact cause-effect relationship is still unclear. This study therefore investigated the causal relationship between SLE and urological cancers using the Mendelian randomization (MR) approach. Our primary MR analysis involved using the inverse variance weighted method, which employed an inverse-variance-weighted approach, to examine the causal relationship between SLE and urological conditions. In addition, we performed various sensitivity analyses, such as MR-Egger regression, tests for heterogeneity, and leave-one-out sensitivity tests, to assess the reliability of our results. The findings from our analysis using Two-Sample MR showed that genetically predicted SLE was linked to a reduced likelihood of developing renal cell carcinoma (RCC) (odds ratio = 0.9996, 95% confidence interval = 0.9993-0.9999, P value = .0159). These results suggest a possible protective impact of SLE against RCC. Nevertheless, no substantial correlation was detected between SLE and the likelihood of developing bladder cancer or prostate cancer. Collectively, these findings offer significant fresh perspectives on the possible correlation between SLE and genitourinary malignancies, specifically RCC, which will provide ideas and basis for the treatment of RCC.

The mechanism of PFK-1 in the occurrence and development of bladder cancer by regulating ZEB1 lactylation

BackgroundBladder cancer (BC) is one of the most common malignancies of the genitourinary system. Phosphofructokinase 1 (PFK-1) is one of member of PFK, which plays an important role in reprogramming cancer metabolism, such as lactylation modification. Zinc finger E-box-binding homeobox 1 (ZEB1) has been demonstrated to be a oncogene in many cancers. Therefore, this study was performed to explore the effects of PFK-1 on the lactylation of ZEB1 in BC development.MethodsCell viability was measured using the CCK-8 kit. The glucose assay kit and lactate assay kit were used to detect glucose utilization and lactate production. The DNA was purified and quantified by qRT-PCR.ResultsIn the present study, we found that ZEB1 expression levels were significantly elevated in bladder cancer cells. Impaired PFK-1 expression inhibits proliferation, migration, and invasion of BC cells and suppresses tumour growth in vivo. We subsequently found that knockdown of PFK-1 decreases glycolysis, including reduced glucose consumption, lactate production and total extracellular acidification rate (ECAR). Mechanistically, PFK-1 inhibits histone lactylation of bladder cancer cells, and thus inhibits the transcription activity of ZEB1.ConclusionOur results suggest that PFK-1 can inhibit the malignant phenotype of bladder cancer cells by mediating the lactylation of ZEB1. These findings suggested PFK-1 to be a new potential target for bladder cancer therapy.

An Atlas of Dietary Intakes and Medication Uses on Risk of Bladder Cancer: A Wide-Angle Mendelian Randomization Analysis

Background Observational studies suggests that diets and medications affect bladder cancer (BC) development, which are subject to confounding and difficult to make causal inference. Here we aimed to investigate whether those observational associations are causal and determining the potential directions and pathways. Methods We used 2-sample Mendelian randomization (MR) analysis to assess associations of dietary intakes, medication uses and molecules with BC risk. Genetic summary data were derived from participants of predominantly European ancestry with rigorous instruments selection, where univariable MR, mediation MR and multivariable MR were performed. Results The results of univariable MR showed 4 dietary intakes and 4 medication uses having a protective effect on BC, while 4 circulating metabolites, 440 circulating proteins and 2 gut microbes were observed to be causally associated with BC risk. Through mediation MR, we found 572 analytes showing consistent mediating effects between dietary intakes or medication uses and BC risk. Furthermore, 9 out of 16 diet-medication pairs showed significant interactions and alterations on BC when consumed jointly. Conclusion In summary, the findings obtained from the current study have important implications for informing prevention strategies that point to potential lifestyle interventions or medication prescriptions to reduce the risk of developing BC. Highlights The current study extends observational literature in showing the importance of diets and medications on bladder cancer prevention. The associations of diets and medications on bladder cancer prevention might be through circulating metabolites, circulating proteins and gut microbiota Our results provide a new understanding of interactions in certain diet-medication pairs which should be taken into account by both physicians and patients during the development of a treatment strategy.

The down-regulation of GADD45B leads to a conversion of cellular oxidative phosphorylation to glycolysis and promotes the progression of bladder cancer

BackgroundThe predominant feature of cancer cells during the process of carcinogenesis is the inclination towards glycolytic metabolism rather than mitochondrial oxidative phosphorylation. Nevertheless, there is a scarcity of research investigating the correlation between bladder cancer and mitochondrial energy metabolism. MethodsA qPCR array comprising 90 genes associated with mitochondrial oxidative phosphorylation was employed to discern metabolic disparities between three sets of bladder cancer tissue and adjacent normal tissue. Wound healing and transwell assays were utilized to assess cell migration and invasion capabilities, respectively. Colony formation assays were conducted to ascertain the tumorigenic potential of the cells. The proliferative capacity of the cells was examined through in vitro CCK-8 assays. Additionally, nude mouse models were established to evaluate the impact of bladder tumor cells on in vivo proliferation. The Seahorse XFe96 Analyzer was utilized to quantify mitochondrial oxidative phosphorylation, while the levels of glucose-6-phosphate and pyruvate were assessed to evaluate glycolysis. ResultsExamination of qPCR array data demonstrated a noteworthy inhibition of mitochondrial oxidative phosphorylation in bladder cancer tissue, as evidenced by the down-regulation of a majority of genes associated with mitochondrial energy metabolism. Notably, GADD45B may potentially exert a significant influence on bladder cancer development, warranting further investigation. The down-regulation of GADD45B in bladder cancer cells resulted in impaired mitochondrial respiration and elevated levels of glycolysis, thereby enhancing cell migration and invasion. Conversely, up-regulation of GADD45B had the opposite effect. Furthermore, over-expression of GADD45B inhibited tumor proliferation and tumorigenesis in both in vitro and in vivo settings. ConclusionThese findings from our study indicate that the down-regulation of GADD45B promotes the shift of cell mitochondrial oxidative phosphorylation towards glycolysis, thereby facilitating the progression of bladder cancer.

Identification of FLRT2 as a key prognostic gene through a comprehensive analysis of TMB and IRGPs in BLCA patients.

The tumor immune environment and immune-related genes are instrumental in the development, progression, and prognosis of bladder cancer (BLCA). This study sought to pinpoint key immune-related genes influencing BLCA prognosis and decipher their mechanisms of action. We analyzed differentially expressed genes (DEGs) between high- and low- tumor mutational burden (TMB) groups. Subsequently, we constructed a reliable prognostic model based on immune-related gene pairs (IRGPs) and analyzed DEGs between high- and low-risk groups. A total of 22 shared DEGs were identified across differential TMB and IRGPs-derived risk groups in BLCA patients. Through univariate Cox and multivariate Cox analyses, we highlighted five genes - FLRT2, NTRK2, CYTL1, ZNF683, PRSS41 - significantly correlated with BLCA patient prognosis. Notably, the FLRT2 gene emerged as an independent prognostic factor for BLCA, impacting patient prognosis via modulation of macrophage infiltration in immune microenvironment. Further investigation spotlighted methylation sites - cg25120290, cg02305242, and cg01832662 - as key regulators of FLRT2 expression. These findings identified pivotal prognostic genes in BLCA and illuminated the intricate mechanisms dictating patient prognosis. This study not only presents a novel prognostic marker but also carves out potential avenues for immunotherapy and targeted therapeutic strategies in BLCA. By demystifying the profound impact of immune-related genes and the tumor immune environment, this study augments the comprehension and prognostic management of bladder cancer.

Redox System and Oxidative Stress-Targeted Therapeutic Approaches in Bladder Cancer.

Bladder cancer (BCa) is the most common genitourinary malignancy, with a high global incidence and recurrence rate that is paired with an increasing caregiver burden and higher financial cost, in addition to increasing morbidity and mortality worldwide. Histologically, BCa is categorized into non-muscle invasive, muscle invasive, and metastatic BCa, on the basis of which the therapeutic strategy is determined. Despite all innovations and recent advances in BCa research, conventional therapies such as chemotherapy, immunotherapy, radiotherapy, and surgery fall short in the complete management of this important malignancy. Besides this worrying trend, the molecular basis of BCa development also remains poorly understood. Burgeoning evidence from experimental and clinical studies suggests that oxidative stress resulting from an imbalance between reactive oxygen species (ROS) generation and the body's antioxidant production plays an integral role in BCa development and progression. Hence, ROS-induced oxidative stress-related pathways are currently under investigation as potential therapeutic targets of BCa. This review focuses on our current understanding regarding ROS-associated pathways in BCa pathogenesis and progression, as well as on antioxidants as potential adjuvants to conventional BCa therapy.

Comprehensive analysis of mitochondria-related genes indicates that PPP2R2B is a novel biomarker and promotes the progression of bladder cancer via Wnt signaling pathway

Bladder cancer (BC) is the fourth and tenth most common malignancy in men and women worldwide, respectively. The complexity of the molecular biological mechanism behind BC is a major contributor to the lack of effective treatment management of the disease. The development and genesis of BC are influenced by mitochondrial retrograde control and mitochondria-nuclear cross-talk. However, the role of mitochondrial-related genes in BC remains unclear. In this study, we analyzed TCGA datasets and identified 752 DE-MRGs in BC samples, including 313 down-regulated MRGs and 439 up-regulated MRGs. Then, the results of machine-learning screened four critical diagnostic genes, including GLRX2, NMT1, PPP2R2B and TRAF3IP3. Moreover, we analyzed their prognostic value and confirmed that only PPP2R2B was associated with clinical prognosis of BC patients and Cox regression assays validated that PPP2R2B expression was a distinct predictor of overall survival in BC patients. Them, we performed RT-PCR and found that PPP2R2B expression was distinctly decreased in BC specimens and cell lines. Functional experiments revealed that overexpression of PPP2R2B distinctly suppressed the proliferation, migration and invasion of BC cells via Wnt signaling pathway. In summary, these research findings offer potential molecular markers for the diagnosis and prognosis of BC, with the discovery of PPP2R2B particularly holding significant biological and clinical significance. This study provides valuable clues for future in-depth investigations into the molecular mechanisms of BC, as well as the development of new diagnostic markers and therapeutic targets.

TM9SF1 promotes bladder cancer cell growth and infiltration.

Bladder cancer (BC) is the most common urological tumor. It has a high recurrence rate, displays tutor heterogeneity, and resists chemotherapy. Furthermore, the long-term survival rate of BC patients has remained unchanged for decades, which seriously affects the quality of patient survival. To improve the survival rate and prognosis of BC patients, it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention. Transmembrane 9 superfamily member 1 (TM9SF1), also known as MP70 and HMP70, is a member of a family of nine transmembrane superfamily proteins, which was first identified in 1997. TM9SF1 can be expressed in BC, but its biological function and mechanism in BC are not clear. To investigate the biological function and mechanism of TM9SF1 in BC. Cells at 60%-80% confluence were transfected with lentiviral vectors for 48-72 h to achieve stable TM9SF1 overexpression or silencing in three BC cell lines (5637, T24, and UM-UC-3). The effect of TM9SF1 on the biological behavior of BC cells was then investigated through CCK8, wound-healing assay, transwell assay, and flow cytometry. Overexpression of TM9SF1 increased the in vitro proliferation, migration, and invasion of BC cells by promoting the entry of BC cells into the G2/M phase. Silencing of TM9SF1 inhibited in vitro proliferation, migration, and invasion of BC cells and blocked BC cells in the G1 phase. TM9SF1 may be an oncogene in BC.

Urinary exosomal mRNA as a biomarker for the diagnosis of bladder cancer.

To study the diagnostic value of mRNA expression in urinary exocrine body in bladder cancer. From February 2022 to December 2022, 60 patients diagnosed with bladder cancer by pathology in the Department of Urology, Affiliated Hospital of Chengde Medical University were selected as the case group. In total, 40 healthy subjects receiving physical examinations were selected as the control group. 100 mL of morning urine samples were collected from the subjects in both groups based on the same standard. Three subjects were randomly selected from each group. Urinary exosomes were extracted by differential ultracentrifugation. High-throughput sequencing (RNA-seq) was used to detect mRNA expression profiles in urinary exosomes and identify differentially expressed genes. Bioinformatic analysis was performed to predict major biological functions of differentially expressed genes and related signaling pathways. RT-PCR validated expression levels of differentially expressed genes in urinary exosomes between the two groups. ROC curves evaluated the diagnostic value of differential genes for bladder cancer. Spearman's correlation analysis determined correlations between differentially expressed genes and the occurrence of bladder cancer. ROC curves speculated the diagnostic value of using combined differentially expressed genes. Compared with normal subjects, there were 189 significantly differentially expressed genes in urinary exosomes of bladder cancer patients, including 33 up-regulated and 156 down-regulated. According to go and kyoto encyclopedia of genes and genomes (KEGG) analysis, the above differentially expressed genes may participate in the occurrence and development of bladder cancer through the MAPK pathway, PPAP signaling pathway, PI3K Akt signaling pathway and Hippo signaling pathway, affect protein and lipid metabolism, RNase activity, polysaccharide synthesis, signal transduction and other biological processes, and participate in cell proliferation, death, movement and adhesion, as well as cell differentiation and signal transduction. RT-PCR verified that the expression of tmeff1, SDPR, ACBD7, SCG2 and COL6A2 in the two groups of samples was statistically significant ( P < 0.05). The ROC curve showed that the area under curve area under the curve of the five differential genes were 0.6934, 0.7746, 0.7239, 0.6396 and 0.6610, respectively. The sensitivity was 42.11%, 64.86%, 47.37%, 73.53% and 76.47%, and the specificity was 90%, 81.36%, 96.36%, 61.02% and 58.18%, respectively. Spearman correlation analysis showed that tmeff1, SDPR and acbd7 were associated with the occurrence of bladder cancer. The ROC curve of the combined diagnosis of the three and the two combined diagnoses suggested that the area under the curve of the combined diagnosis of SDPR and acbd7 was 0.7945, the sensitivity was 89.09%, and the specificity was 60.53%. The gene expression profile in urinary exosomes of bladder cancer patients has changed significantly, and the differential genes may play an important biological role in the occurrence and development of bladder cancer. The combined detection of urinary exosome SDPR and ACBD7 has a certain diagnostic value for bladder cancer.

Occupational exposure to organic solvents and risk of bladder cancer.

Bladder cancer has been linked to several occupations that involve the use of solvents, including those used in the dry-cleaning industry. We evaluated exposure to solvents and risk of bladder cancer in 1182 incident cases and 1408 controls from a population-based study. Exposure to solvents was quantitatively assessed using a job-exposure matrix (CANJEM). Exposure to benzene, toluene and xylene often co-occur. Therefore, we created two additional sets of metrics for combined benzene, toluene and xylene (BTX) exposure: (1) CANJEM-based BTX metrics and (2) hybrid BTX metrics, using an approach that integrates the CANJEM-based BTX metrics together with lifetime occupational histories and exposure-oriented modules that captured within-job, respondent-specific details about tasks and chemicals. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) were estimated using logistic regression. Bladder cancer risks were increased among those ever exposed to benzene (OR = 1.63, 95% CI: 1.14-2.32), toluene (OR = 1.60, 95% CI: 1.06-2.43), and xylene (OR = 1.67, 95% CI: 1.13-2.48) individually. We further observed a statistically significant exposure-response relationship for cumulative BTX exposure, with a stronger association using the hybrid BTX metrics (ORQ1vsUnexposed = 1.26, 95% CI: 0.83-1.90; ORQ2vsUnexposed = 1.52, 95% CI: 1.00-2.31; ORQ3vsUnexposed = 1.88, 95% CI: 1.24-2.85; and ORQ4vsUnexposed = 2.23, 95% CI: 1.35-3.69) (p-trend=0.001) than using CANJEM-based metrics (p-trend=0.02). There is limited evidence about the role of exposure to specific organic solvents, alone or in combination on the risk of developing bladder cancer. In this study, workers with increasing exposure to benzene, toluene, and xylene as a group (BTX) had a statistically significant exposure-response relationship with bladder cancer. Future evaluation of the carcinogenicity of BTX and other organic solvents, particularly concurrent exposure, on bladder cancer development is needed.

Regulatory Role of Autophagy and Glucose Metabolic Reprogramming in the Malignant Progression of Bladder Cancer: A Review

Bladder cancer is a common malignant tumor of urinary system. Due to the rise of China's aging population, there is an increased pressure on the diagnosis and treatment of bladder cancer continues to increase. Unfortunately, the mechanism(s) of malignant progression of bladder cancer is still unclear, and the current treatment modality for patients with advanced bladder cancer are very limited and the benefits are not obvious. It is urgent to explore the mechanisms of cancer progression, so as to delay, block or even reverse its course more effectively. Autophagy and reprogramming of glucose metabolism play a very important regulatory role in the malignant development of bladder cancer such as proliferation, drug resistance, invasion and metastasis, and autophagy has been found in other solid tumors to regulate glucose metabolism and influence the malignant progression of tumors. This article highlights the regulation of autophagy and glucose metabolism reprogramming in the development of bladder cancer.