Urothelial Carcinoma Of Bladder Research Articles

Specific subsets of urothelial bladder carcinoma infiltrating T cells associated with poor prognosis

Comprehensive investigation of tumor-infiltrating lymphocytes in cancer is crucial to explore the effective immunotherapies, but the composition of infiltrating T cells in urothelial bladder carcinoma (UBC) remains elusive. Here, single-cell RNA sequencing (scRNA-seq) were performed on total 30,905 T cells derived from peripheral blood, adjacent normal and tumor tissues from two UBC patients. We identified 18 distinct T cell subsets based on molecular profiles and functional properties. Specifically, exhausted T (TEx) cells, exhausted NKT (NKTEx) cells, Ki67+ T cells and B cell-like T (B-T) cells were exclusively enriched in UBC. Additionally, the gene signatures of TEx, NKTEx, Ki67+ T and B-T cells were significantly associated with poor survival in patients with BC and various tumor types. Finally, IKZF3 and TRGC2 are the potential biomarkers of TEx cells. Overall, our study demonstrated an exhausted context of T cells in UBC, which layed a theoretical foundation for the development of effective tumor immunotherapies.

A novel model based on disulfidptosis-related genes to predict prognosis and therapy of bladder urothelial carcinoma.

Disulfidptosis is a novel type of cell death induced by disulphide stress that depends on the accumulation of cystine disulphide, causing cytotoxicity and triggering cell death. However, the direct prognostic effect and regulatory mechanism of disulfidptosis-related genes in bladder urothelial carcinoma (BLCA) remain unclear. To explore the role of 10 disulfidptosis-related genes, the multiomic data of 10 genes were comprehensively analysed. Next, based on seven disulfidptosis-related differentially expressed genes, a novel disulfidptosis-related gene score was developed to help predict the prognosis of BLCA. Immunohistochemistry, EDU, Real-time PCR and western blot were used to verify the model. Significant functional differences were found between the high- and low-risk score groups, and samples with a higher risk score were more malignant. Furthermore, the tumour exclusion and Tumour Immune Dysfunction and Exclusion scores of the high-risk score group were higher than those of the low-risk score group. The risk score was positively correlated with the expression of immune checkpoints. Drug sensitivity analyses revealed that the low-risk score group had a higher sensitivity to cisplatin, doxorubicin, docetaxel and gemcitabine than the high-risk score group. Moreover, the expression of the TM4SF1 was positively correlated with the malignancy degree of BLCA, and the proliferation ability of BLCA cells was reduced after knockdown TM4SF1. The present study results suggest that disulfidptosis-related genes influence the prognosis of BLCA through their involvement in immune cell infiltration. Thus, these findings indicate the role of disulfidptosis in BLCA and its potential regulatory mechanisms.

Clinical neutrophil-related gene helps treat bladder urothelial carcinoma

Abstract Objectives Most researches have shown that neutrophils are closely related to bladder urothelial carcinoma (BLCA), especially its occurrence and development. Although tumor microenvironment (TME) related genes have an impact on prognosis, the role of neutrophil related genes in BLCA adjuvant therapy is not clear. Methods We used sample information from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases. And we utilized the CIBERSORT algorithm to obtain the tumor immune microenvironment (TIME) landscape and weighted gene co-expression network analysis (WCGNA) to detect neutrophil-related gene modules. We used univariate Cox regression, multivariate Cox regression, and lasso regression analyses to identify genes that have a relationship with BLCA prognosis. Using the median risk score (RS), we classified the cohort into a high-risk group (HRG) and low-risk group (LRG). External validation of RS was performed via GEO data feeds. Prognostic nomograms were constructed with reference to RS and clinically relevant information and validated using calibration curves. We analyzed the latent connections between RS and tumor mutational burden. Finally, the latent associations between risk markers and chemotherapy prognosis were explored using the pRRophetic algorithm. Results In this study, 10 TME-related genes with important prognostic value were screened. Then, by deriving the RS, we constructed a prognostic risk prediction nomogram using parameters such as sex, age, TNM stage, clinical stage, and RS. The area under the receiver operating characteristic curve showed that the predictive accuracy of the constructed nomogram was high. We found that using immunotherapy with new immune checkpoint inhibitors (ICIs) was more beneficial for patients in the LRG. In addition, we can learn from the chemotherapeutic drug model that patients with LRG are more sensitive to cisplatin and imatinib. Conclusions In short, the prognostic prediction model based on neutrophil-related genes will help to predict the prognosis and guide the precise treatment of BLCA.

TUBA1C is a potential new prognostic biomarker and promotes bladder urothelial carcinoma progression by regulating the cell cycle

BackgroundTUBA1C is an α-tubulin isoform involved in mitosis, and its dysregulation has been implicated in tumor progression. There is still no clear understanding of its role in bladder urothelial carcinoma (BLCA).MethodsThis study examined the differential expression of TUBA1C and its prognostic significance in bladder cancer based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) and also assessed the correlation of TUBA1C expression level with immune cell infiltration and immune checkpoint gene expression levels and the half-inhibitory concentration (IC50) of different chemotherapeutic agents. Immunotherapy response was estimated using the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm. We detected TUBA1C expression in BLCA cells using PCR and Western blotting. Functional assays, including CCK-8, colony formation, transwell, apoptosis and cell cycle assays, were also performed to assess the oncogenic role of TUBA1C in BLCA.ResultIn three independent public cohorts, TUBA1C was significantly upregulated in bladder tumor tissues, and high TUBA1C expression in bladder cancer was associated with a poorer outcome than low expression. TUBA1C was an independent prognostic risk factor for bladder cancer, and numerous immune checkpoint genes and infiltrating immune cells were associated with TUBA1C. TIDE analysis revealed that TUBA1C showed great potential for predicting the immunotherapy response in bladder cancer patients. In addition, drug sensitivity analysis revealed that high TUBA1C expression indicated sensitivity to multiple chemotherapeutic agents. Functional assays revealed that silencing TUBA1C significantly inhibited the proliferation, migration and invasion of BLCA cells and induced apoptosis and cell cycle arrest.ConclusionThe overexpression of TUBA1C in bladder cancer predicts a poor prognosis and may also be a potential immunotherapeutic target. As a prognostic marker, TUBA1C influences tumor progression by regulating the cell cycle.

A case of bladder urothelial carcinoma nested variant with invasion to the rectum treated with surgery and intraoperative radiotherapy.

A case of bladder urothelial carcinoma nested variant with invasion to the rectum treated with surgery and intraoperative radiotherapy.

Molecular classification of urothelial bladder carcinoma.

Urothelial bladder carcinoma (UC) ranks among the top ten most commonly diagnosed cancers worldwide on an annual basis. The standardized classification system for urothelial bladder tumors is the Tumor, Node, Metastasis classification, which reflects differences between non-muscle-invasive bladder carcinoma (NMIBC) and muscle-invasive bladder carcinoma (MIBC) and it depends on the extent to which tumor has infiltrated the bladder wall and other tissues and organs. NMIBC and MIBC exhibit great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. In recent years, studies based on mRNA expression profiling revealed the existence of biologically relevant molecular subtypes of UC, which show variant molecular features that can provide more precise stratification of UC patients. Here, we present a complex classification of UC based on mRNA expression studies and molecular subtypes of NMIBC and MIBC in detail with regard to different mRNA expression profiles, mutational signatures, and infiltration by non-tumor cells. The possible impact of molecular subtyping on treatment decisions and patients' outcomes is outlined, too.

Pan-cancer and single-cell analysis reveal the prognostic value and immune response of NQO1.

Background: Overexpression of the NAD(P)H: Quinone Oxidoreductase 1 (NQOI) gene has been linked with tumor progression, aggressiveness, drug resistance, and poor patient prognosis. Most research has described the biological function of the NQO1 in certain types and limited samples, but a comprehensive understanding of the NQO1's function and clinical importance at the pan-cancer level is scarce. More research is needed to understand the role of NQO1 in tumor infiltration, and immune checkpoint inhibitors in various cancers are needed. Methods: The NQO1 expression data for 33 types of pan-cancer and their association with the prognosis, pathologic stage, gender, immune cell infiltration, the tumor mutation burden, microsatellite instability, immune checkpoints, enrichment pathways, and the half-maximal inhibitory concentration (IC50) were downloaded from public databases. Results: Our findings indicate that the NQO1 gene was significantly upregulated in most cancer types. The Cox regression analysis showed that overexpression of the NQO1 gene was related to poor OS in Glioma, uveal melanoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma, and adrenocortical carcinoma. NQO1 mRNA expression positively correlated with infiltrating immune cells and checkpoint molecule levels. The single-cell analysis revealed a potential relationship between the NQO1 mRNA expression levels and the infiltration of immune cells and stromal cells in bladder urothelial carcinoma, invasive breast carcinoma, and colorectal cancer. Conversely, a negative association was noted between various drugs (17-AAG, Lapatinib, Trametinib, PD-0325901) and the NQO1 mRNA expression levels. Conclusion: NQO1 expression was significantly associated with prognosis, immune infiltrates, and drug resistance in multiple cancer types. The inhibition of the NQO1-dependent signaling pathways may provide a promising strategy for developing new cancer-targeted therapies.

Artificial Intelligence to Predict the BRAF V595E Mutation in Canine Urinary Bladder Urothelial Carcinomas.

In dogs, the BRAF mutation (V595E) is common in bladder and prostate cancer and represents a specific diagnostic marker. Recent advantages in artificial intelligence (AI) offer new opportunities in the field of tumour marker detection. While AI histology studies have been conducted in humans to detect BRAF mutation in cancer, comparable studies in animals are lacking. In this study, we used commercially available AI histology software to predict BRAF mutation in whole slide images (WSI) of bladder urothelial carcinomas (UC) stained with haematoxylin and eosin (HE), based on a training (n = 81) and a validation set (n = 96). Among 96 WSI, 57 showed identical PCR and AI-based BRAF predictions, resulting in a sensitivity of 58% and a specificity of 63%. The sensitivity increased substantially to 89% when excluding small or poor-quality tissue sections. Test reliability depended on tumour differentiation (p < 0.01), presence of inflammation (p < 0.01), slide quality (p < 0.02) and sample size (p < 0.02). Based on a small subset of cases with available adjacent non-neoplastic urothelium, AI was able to distinguish malignant from benign epithelium. This is the first study to demonstrate the use of AI histology to predict BRAF mutation status in canine UC. Despite certain limitations, the results highlight the potential of AI in predicting molecular alterations in routine tissue sections.

Comprehensive analysis of cuproptosis-related lncRNAs signature to predict prognosis in bladder urothelial carcinoma

BackgroundCuproptosis-related genes (CRGs) have been recently discovered to regulate the occurrence and development of various tumors by controlling cuproptosis, a novel type of copper ion-dependent cell death. Although cuproptosis is mediated by lipoylated tricarboxylic acid cycle proteins, the relationship between cuproptosis-related long noncoding RNAs (crlncRNAs) in bladder urothelial carcinoma (BLCA) and clinical outcomes, tumor microenvironment (TME) modification, and immunotherapy remains unknown. In this paper, we tried to discover the importance of lncRNAs for BLCA.MethodsThe BLCA-related lncRNAs and clinical data were first obtained from The Cancer Genome Atlas (TCGA). CRGs were obtained through Coexpression, Cox regression and Lasso regression. Besides, a prognosis model was established for verification. Meanwhile, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, gene ontology (GO) analysis, principal component analysis (PCA), half-maximal inhibitory concentration prediction (IC50), immune status and drug susceptibility analysis were carried out.ResultsWe identified 277 crlncRNAs and 16 survival-related lncRNAs. According to the 8-crlncRNA risk model, patients could be divided into high-risk group and low-risk group. Progression-Free-Survival (PFS), independent prognostic analysis, concordance index (C-index), receiver operating characteristic (ROC) curve and nomogram all confirmed the excellent predictive capability of the 8-lncRNA risk model for BLCA. During gene mutation burden survival analysis, noticeable differences were observed in high- and low-risk patients. We also found that the two groups of patients might respond differently to immune targets and anti-tumor drugs.ConclusionThe nomogram with 8-lncRNA may help guide treatment of BLCA. More clinical studies are necessary to verify the nomogram.

Robot-assisted cystectomy in treatment of patients with bladder urothelial carcinoma

The article presents an assessment of the results of surgical treatment of bladder urothelial carcinoma using the Da Vinci Si robotic system. The experience of treating 11 patients who underwent robot-assisted cystectomy (RACE) was analysed. This study demonstrates the effectiveness of RACE due to minimal trauma, blood loss, transfusion frequency, and length of patient stay in the hospital.

Study of her2/neu and ki-67 expression in invasive urothelial carcinoma of bladder and their correlation with grade and stage

Urinary bladder cancer is one of the costliest diseases, which requires lifelong surveillance due to its rapid aggressive clinical course. Here, HER2/neu and Ki-67 expression, is studied, as important prognostic marker with therapeutic implications in invasive urothelial bladder carcinoma (IUBC). To study expression of HER2/neu and Ki-67 in histologically diagnosed cases of IUBC and their clinicopathological correlation.An observational, cross-sectional, study was performed in Pathology Department, NRS Medical College, Kolkata, from February 2020 to July 2021. Tissue sections, after proper processing, were stained in H&amp;E. A total of 75 IUBC cases were histopathologically diagnosed with grade and stage. HER2/neu and Ki-67 expression by immunohistochemistry was studied in them; which was compared with clinicopathological variables like age, sex, risk factors, histological type, grade, stage, etc. Statistical analysis software EPI INFO (TM) 7.2.2.2 was used, p&amp;#60;0.05 was taken to be statistically significant.Among 75 cases of IUBC, 60% were high grade and 72% were of lower (pT1) stage. HER2/neu was positive in 52% cases; significantly associated with males, haematuria, smoking, necrosis, high grade (p&amp;#60;0.00001) and higher stage (pT2/3/4) (p=0.0005). Ki-67 index was high in 56% cases; significantly associated with &amp;#62;50 years age group, haematuria, smoking, necrosis, LVI, high grade (p&amp;#60;0.00001) and higher stage (p&amp;#60;0.0001). Positive HER2/neu expression was also significantly associated with high Ki-67 index (p&amp;#60;0.00001).Positive HER2/neu expression and high Ki-67 index is significantly associated with high grade and stage of tumours. So, these patients may be considered for targeted therapy using Trastuzumab in addition to conventional therapy.

Pathologic collision of urinary bladder urothelial carcinoma with small cell carcinoma: a case report

BackgroundUrothelial carcinoma is a major subtype of bladder cancer and small cell carcinoma (SCC) is a rare type of cancer in clinical practice. Pathologic collision of urinary bladder urothelial carcinoma with SCC is not common in clinical settings.Case presentationHere, we report a patient with high-grade papillary carcinoma which changed to collision tumor with SCC. The patient underwent radical cystectomy; however, neck and mediastinum lymph nodes metastases were detected 11 months after the operation. The lymph nodes were diagnosed pathologically as SCC. Chemoradiotherapy was subsequently prescribed. Unfortunately, this patient died of COVID-19 in early 2023.DiscussionWe hypothesized the mechanism underlying this pathological transformation. For patients with urothelial bladder cancer, pathological analysis should be conducted to allow standardized and persistent treatment. Moreover, drugs should be selected depending on the type of pathology, especially for patients who develop relapse, since collision tumor or other pathological tumors may be present.ConclusionsWe recommend that radical cystectomy be performed early enough for patients with non-muscle invasive bladder cancer, who are at a high risk of tumor recurrence. However, this conclusion needs to be validated in a larger number of patients.

Interobserver agreement and the role of smoothelin immunostain in the evaluation of Muscularis Propria (MP) invasion of Bladder Urothelial Carcinoma (BUC)

Link of Video Abstract: https://youtu.be/KymxBUAr9eIBackground: Bladder Urothelial Carcinoma (BUC) is common cancer in the genitourinary organs. One important determinant for its therapy modality is the presence of tumor invasion into Muscularis Propria (MP). Assessing MP invasion in routine Hematoxylin-Eosin (HE) slides of Transurethral Resection of Bladder (TUR-B) specimens is not always easy due to tissue fragmentation and morphological similarities of MP to muscularis mucosa (MM) and myofibroblasts. This study was done to determine the interobserver agreement in evaluating MP invasion and to find alternatives to overcome this diagnostic problem. Methods: This cross-sectional observational analytic study was conducted in the Pathology Laboratory of the Faculty of Medicine, Universitas Udayana/Prof. Dr. I.G.N.G. Ngoerah Hospital, Bali, in 2022. As many as 72 HE slides of TUR-B specimens of BUC patients were examined separately by five experienced pathologists. Smoothelin immunostaining, a marker to identify MP, was also examined as a comparison. Data were processed and statistically tested using the SPSS version 20.0 program for Windows. Results: The interobserver agreement of those five pathologists was found to be low to moderate, with an average = 0.48, ranging between 0.18-0.69. One pathologist had a low agreement with four others (&lt;0.4) and indicated diagnostic uncertainty in 41% of the samples examined. Among four other pathologists, the agreements were moderate, with = 0.40-0.69. The proportion of concordant examination results was only 45.8%. When the outcome of each HE slide was concluded by consensus, it was found that there was no statistically significant difference with smoothelin immunostaining results. Conclusion: Evaluation of MP invasion of BUC in TUR-B specimens had low to moderate interobserver agreement, which indicated that this examination was subjective. However, the consensus of several pathologists seems to lead to better accuracy, close to the result of smoothelin immunostaining.

Identification of a cancer-associated fibroblast signature for predicting prognosis and immunotherapeutic responses in bladder urothelial carcinoma

Background Cancer-associated fibroblasts (CAFs) are the most important cellular components in bladder urothelial carcinoma (BLCA) and are involved in the development and immunosuppression of BLCA. Therefore, we aimed to construct a CAF-associated signature for predicting the prognosis and immunotherapy response in patients with BLCA. Methods CAF infiltration and stromal score were quantified using two algorithms. Weighted gene co-expression network analysis (WGCNA) was performed to identify the CAF-associated modules and hub genes. Univariate Cox and Least Absolute Shrinkage and Selection Operator regression analyses were used for constructing CAF signatures and calculating CAF scores. The ability of the CAF signature to predict prognosis and response to immunotherapy was validated using the data from three cohorts. Results WGCNA identified two CAF-associated modules and constructed a CAF signature containing 27 genes. In all three cohorts, patients with high CAF scores had markedly worse prognoses than those with low CAF scores, and CAF scores were independent risk factors. In addition, patients with high CAF scores did not respond to immunotherapy, whereas those with lower CAF scores responded to immunotherapy. Conclusion CAF signature can be used to predict prognosis and immunotherapy response to guide individualized treatment planning in patients with BLCA.

Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma.

The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers' expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

Neoadjuvant Chemotherapy Prior to Radical Cystectomy for Muscle-Invasive Bladder Cancer With Variant Histology: A Systematic Review and Meta-Analysis of Survival Outcomes and Pathological Features

PurposeTo conduct systematic review and meta-analysis to evaluate effects of neoadjuvant chemotherapy (NAC) on survival and histopathological outcomes of variant histology (VH) of urothelial carcinoma (UC) of bladder. MethodsThis systematic review was registered in PROSPERO (CRD42023389115). Literature search was conducted in PubMed/Medline, Embase, and Cochrane Library for studies published up to January 2023. Population, intervention, comparator, outcome, and study design were as follows: bladder cancer patients with VH (population), neoadjuvant chemotherapy (intervention), radical cystectomy only (comparators), oncological survival and pathologic response (outcomes), and retrospective or prospective (study design). ResultsFinally, a total of 17 studies were included in the present study (quantitative analysis, n = 17; qualitative analysis, n = 12). Pooled HR was 0.49 (95% CI: 0.31-0.76; P = .002) for OS. Pooled HR was 0.61 (95% CI: 0.38-0.98; P = .04) for CSS. Pooled HR was 0.44 (95% CI: 0.21-0.93; P = .03) in PFS. Pooled OR was 6.61 (95% CI: 4.50-9.73; P < .00001) in complete pathologic response. Pooled OR was 9.59 (95% CI: 3.56-25.85; P < .00001) in any pathologic response. Evidence quality assessments for each 5 comparisons using the GRADE approach were that Certainty was moderate in 1, low in 1, and very low in 3. ConclusionsAdministration of NAC before surgery in bladder cancer patients with VH might confer better survival outcomes and higher pathologic down staging rate than no administration of NAC before surgery.

Identification of novel lncRNA prognostic biomarkers and their associated ceRNAs in bladder urothelial carcinoma.

Bladder urothelial carcinoma (BUCA) is a common malignant tumor with a high rate of metastasis and recurrence. The lack of specific and sensitive biomarkers for the prognostic assessment makes it important to seek alternatives. Recent studies have demonstrated that long noncoding RNAs (lncRNAs) function as competitive endogenous RNAs (ceRNAs) and play an important role in BUCA prognosis. Therefore, this study aimed to establish a prognosis-related lncRNAs-microRNAs (miRNAs)-messenger RNA (mRNA) (pceRNA) network and identify novel prognostic biomarkers. Integrated weighted coexpression analysis, functional clustering, and ceRNA network were used for the prognostic assessment of BUCA. The transcriptome sequencing datasets of lncRNA, miRNA, and mRNA from The Cancer Genome Atlas database were used for the identification of key lncRNAs and construction of the lncRNAs expression signature for prognostic prediction of BUCA patients. Then, 14 differentially expressed lncRNAs (DE-lncRNAs) were identified as candidate prognostic RNAs based on the ceRNAs network and functional clustering. In the Cox regression analysis, two (AC008676.1 and ADAMTS9-AS1) of all DE-lncRNAs were significantly associated with overall survival (OS) of BUCA patients. This two DE-lncRNA signature was significantly correlated with OS and was an independent prognostic factor, which was confirmed in an independent dataset of GSE216037. Moreover, we constructed the pceRNA network that includes 2 DE-lncRNAs, 9 DE-miRNAs, and 10 DE-mRNAs. Pathway enrichment analysis showed that AC008676.1 and ADAMTS9-AS1 are involved in several cancer-related pathways such as proteoglycans in cancer and TGF-beta signaling pathway. The novel-identified DE-lncRNA prognostic signature and the pceRNA network in this study will be valuable risk predictors and diagnostic markers for BUCA.

Immunohistochemical Expression of Estrogen Receptor Beta in Urothelial Carcinoma of the Urinary Bladder

Immunohistochemical Expression of Estrogen Receptor Beta in Urothelial Carcinoma of the Urinary Bladder

Upregulation of dihydropyrimidinase-like 3 (DPYSL3) protein predicts poor prognosis in urothelial carcinoma

BackgroundDihydropyrimidinase-like 3 (DPYSL3) is a cytosolic phosphoprotein expressed in the nervous system and is crucial for neurogenesis. A previous study showed that increased DPYSL3 expression promotes tumour aggressiveness in pancreatic ductal adenocarcinoma, gastric cancer, and colon cancer. However, the role of DPYSL3 in affecting the biological behaviour of urothelial carcinoma (UC) is not yet understood.MethodsA UC transcriptomic dataset from the Gene Expression Omnibus and the Urothelial Bladder Cancer (BLCA) dataset from The Cancer Genome Atlas were used for the in silico study. We collected 340 upper urinary tract urothelial carcinoma (UTUC) and 295 urinary bladder urothelial carcinoma (UBUC) samples for the immunohistochemical study. Fresh tumour tissue from 50 patients was used to examine the DPYSL3 mRNA level. In addition, urothelial cell lines with and without DPYSL3 knockdown were used for the functional study.ResultsThe in silico study revealed that DPYSL3 correlated with advanced tumour stage and metastasis development while functioning primarily in the nucleobase-containing compound metabolic process (GO:0006139). DPYSL3 mRNA expression is significantly upregulated in advanced UC. Furthermore, overexpression of the DPYSL3 protein is significantly associated with the aggressive behaviour of UTUC and UBUC. DPYSL3 expression independently predicts disease-specific survival (DSS) and metastatic-free survival (MFS) in patients with UC. In non-muscle-invasive UBUC, DPYSL3 expression predicts local recurrence-free survival. UC cell lines with DPYSL3 knockdown exhibited decreased proliferation, migration, invasion, and human umbilical vein endothelial cells (HUVECs) tube formation but increased apoptosis and G1 arrest. Gene ontology enrichment analysis revealed that the enriched processes related to DPYSL3 overexpression in UC were tissue morphogenesis, cell mesenchyme migration, smooth muscle regulation, metabolic processes, and RNA processing. In vivo study revealed DPYSL3 knockdown in UC tumours significantly suppressed the growth of tumours and decreased MYC and GLUT1 protein expression.ConclusionsDPYSL3 promotes the aggressiveness of UC cells by changing their biological behaviours and is likely associated with cytoskeletal and metabolic process modifications. Furthermore, DPYSL3 protein overexpression in UC was associated with aggressive clinicopathological characteristics and independently predicted poor clinical outcomes. Therefore, DPYSL3 can be used as a novel therapeutic target for UC.

CCNB1 is involved in bladder cancer pathogenesis and silencing CCNB1 decelerates tumor growth and improves prognosis of bladder cancer.

In search of an effective therapeutic target for bladder urothelial carcinoma (BLCA), the present study aimed to investigate the expression of cyclin B1 (CCNB1) and its putative mechanism in BLCA. BLCA sequencing data from Gene Expression Omnibus and The Cancer Genome Atlas were used to analyze expression of CCNB1 mRNA and high CCNB1 expression had a poorer prognosis compared with those with low expression. Immunohistochemistry (IHC) samples collected from the Human Protein Atlas database were analyzed for CCNB1 protein expression. Short hairpin (sh) CCNB1-transfected BLCA T24 and 5637 cells were used to investigate the effects of CCNB1 and inhibit the proliferation, migration and invasion of BLCA cells, affect the cell cycle distribution and promote apoptosis of 5637 cells. A sh-CCNB1 BLCA chicken embryo chorioallantoic membrane (CAM) transplantation model was established to observe the impacts of sh-CCNB1 on the tumorigenesis of BLCA in vivo. Analysis of sequencing data showed that CCNB1 mRNA was significantly elevated in tumor and BLCA compared with normal tissues [standardized mean difference (SMD)=1.21; 95% CI: 0.26-2.15; I²=95.9%]. IHC indicated that CCNB1 protein was localized in the nucleus and cytoplasm and was significantly increased in BLCA tumor tissues. The in vitro tests demonstrated that proliferation of T24 and 5637 cells transfected with sh-CCNB1 was significantly inhibited and cell migration and invasion ability were significantly decreased. sh-CCNB1 decreased the percentage of T24 cells in G0/G1, 5637 cells in the G0/G1 phase and S phase and increased percentage of 5637 cells in the G2/M phase and increased early apoptosis of 5637 cells. The in vivo experiments demonstrated that the mass of transplanted tumors was significantly decreased compared with the control group following silencing of CCNB1. The present results suggested that CCNB1 was involve in the development and prognosis of BLCA and silencing of CCNB1 may be a promising targeted therapy for BLCA.