Development Of Bladder Cancer Research Articles

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.

Roles of Androgen Receptor Signaling in Urothelial Carcinoma.

Preclinical and clinical data suggest that androgen receptor signaling strongly contributes to bladder cancer development. The roles of the androgen receptor in bladder carcinogenesis have obvious implications for understanding the strong male sex bias in this disease and for potential therapeutic strategies as well. In this review, we summarize what is known about androgen receptor signaling in urothelial carcinoma as well as in tumor-infiltrating immune cells, reviewing preclinical and clinical data. We also highlight clinical trial efforts in this area.

FATP2 activates PI3K/Akt/mTOR pathway by inhibiting ATF3 and promotes the occurrence and development of bladder cancer

Bladder cancer (BLCA) is ranked among the main causes of mortality in male cancer patients, and research into targeted therapies guided by its genomics and molecular biology has been a prominent focus in BLCA studies. Fatty acid transporter protein 2 (FATP2), a member of the FATPs family,is a key contributor to the progression of cancers such as hepatocellular carcinomas and melanomas.However,its role in BLCA remains poorly understand. This study delved into the function of FATP2 in BLCA through a succession of experiments in vivo and in vitro, employing techniques as quantitative real-time polymerase chain reaction (qRT-PCR), RNA sequencing, transwell assays, immunofluorescence, western blot,and others to dissect its mechanistic actions. The findings revealed that an oncogenic function is executed by FATP2 in bladder cancer, significantly impacting the proliferation and migration capabilities, thereby affecting the prognosis of BLCA patients. Furthermore, A suppression that relies on both time and concentration of BLCA proliferation and migration, trigger of apoptosis, and blockage of the cell cycle at the G2/M phase were observed when the inhibitor of FATP2, Lipofermata, was applied. It was unveiled through subsequent investigations that ATF3 expression is indirectly promoted by Lipofermata through the inhibition of FATP2, ultimately inhibiting the signal transduction of the PI3K/Akt/mTOR pathway. This effect was also responsible for the inhibitory impact on BLCA proliferation. Therefore, FATP2 emerges as an auspicious and emerging molecular target with potential applications in precision therapy in BLCA.

Identification and preliminary analysis of hub genes associated with bladder cancer progression by comprehensive bioinformatics analysis

Bladder cancer (BC) is a crisis to human health. It is necessary to understand the molecular mechanisms of the development and progression of BC to determine treatment options. Publicly available expression data were obtained from TCGA and GEO databases to spot differentially expressed genes (DEGs) between cancer and normal bladder tissues. Weighted co-expression networks were constructed, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Associations in hub genes, immune infiltration, and immune therapy were evaluated separately. Protein–protein interaction (PPI) networks for the genes identified in the normal and tumor groups were launched. 3461 DEGs in the TCGA dataset and 1069 DEGs in the GSE dataset were identified, including 87 overlapping genes between cancer and normal bladder groups. Hub genes in the tumor group were mainly enriched for cell proliferation, while hub genes in the normal group were related to the synthesis and secretion of neurotransmitters. Based on survival analysis, CDH19, RELN, PLP1, and TRIB3 were considerably associated with prognosis (P < 0.05). CDH19, RELN, PLP1, and TRIB3 may play important roles in the development of BC and are potential biomarkers in therapy and prognosis.

Expression, Prognostic Value, and Immune Infiltration of MTHFD Family in Bladder Cancer.

The Methylenetetrahydrofolate Dehydrogenase (MTHFD) family plays an important role in the development and prognosis of a variety of tumors; however, the role of the MTHFD family in bladder cancer is unclear. R software, cBioPortal, GeneMANIA, and online sites such as String-LinkedOmics were used for bioinformatics analysis. MTHFD1/1L/2 was significantly upregulated in bladder cancer tissues compared with normal tissues, high expression of the MTHFD family was strongly associated with poorer clinical grading and staging, and bladder cancer patients with upregulated expression of MTHFD1L/2 had a significantly worse prognosis. Gene function and PPI network analysis revealed that the MTHFD family and related genes play synergistic roles in the development of bladder cancer. 800 co-expressed genes related to the MTHFD family were used for functional enrichment analysis, and the results showed that many genes were associated with various oncogenic pathways such as cell cycle and DNA replication. More importantly, the MTHFD family was closely associated with multiple infiltrating immune lymphocytes, including Treg cells, and immune molecules such as TNFSF9, CD274, and PDCD1. Our study shows that MTHFD family genes may be potential prognostic markers and therapeutic targets for patients with bladder cancer.