Potential Biomarkers For Bladder Cancer Research Articles

Unveiling urinary extracellular vesicle mRNA signature for early diagnosis and prognosis of bladder cancer.

Background: Bladder cancer (BC) ranks as one of the most prevalent cancers. Its early diagnosis is clinically essential but remains challenging due to the lack of reliable biomarkers. Extracellular vesicles (EVs) carry abundant biological cargoes from parental cells, rendering them as promising cancer biomarkers. Herein, we revealed that urinary EVs (uEVs) mRNA signature could serve as non-invasive biomarker for the early diagnosis and prognostic assessment for BC. Methods: Transcriptomic sequencing was conducted to reveal the mRNA signature of EVs collected from normal cell line and different grades of BC cell lines. Candidate EV-mRNA biomarkers were further profiled using clinical urine samples (n = 97, including healthy controls, BC patients and post-surgery BC patients) by RT-qPCR. Results: Three mRNAs (SRGN, FLI1, and MACROH2A2) within uEV were identified as potential biomarkers for BC, providing an area under the receiver operating characteristic curve (AUC) of 0.973 for BC diagnosis. Moreover, the uEV-mRNA panel could discriminate early-stage BC patients from healthy controls with an AUC of 0.969. Finally, we found that the uEV-mRNAs were significantly down-regulated in the post-surgery urine samples of BC patients. Conclusions: Given the facile and non-intrusive nature of urine collection, the identified uEV-mRNAs could serve as potential liquid-biopsy biomarkers for the early diagnosis and prognosis of BC.

Identifying Prostaglandin D2 Synthase in Urine: A Potential Biomarker for Bladder Cancer

Identifying Prostaglandin D2 Synthase in Urine: A Potential Biomarker for Bladder Cancer

Dysbiosis in Human Urinary Microbiota May Differentiate Patients with a Bladder Cancer.

Recent interest in noninvasive diagnostic approaches has highlighted the potential of urinary microbiota as a novel biomarker for bladder cancer. This study investigated the urinary microbiota of 30 bladder cancer patients and 32 healthy controls using a specific NGS protocol that sequences eight hypervariable regions of the 16S rRNA gene, providing detailed insights into urinary microbiota composition. The relative abundance of microbial compositions in urine samples from cancer patients and healthy controls was analyzed across various taxonomic levels. No notable differences were highlighted at the phylum, class, order, and family levels. At the genus level, 53% of detected genera were represented in either cancer patients or healthy controls. Microbial diversity was significantly lower in cancer patients. The differential analysis identified five genera, Rhodanobacter, Cutibacterium, Alloscardovia, Moryella, and Anaeroglobus, that were significantly more abundant in cancer patients. Notably, Rhodanobacter was present in 20 cancer samples but absent in healthy controls. Conversely, 40 genera, including Lactobacillus, Propionibacterium, and Bifidobacterium, exhibited reduced abundance in cancer patients. These findings suggest that some genera may serve as potential biomarkers for bladder cancer, highlighting the need for further research to explore their roles in disease pathogenesis and their potential applications in diagnostics and therapeutics.

Uncovering Microbial Composition of the Tissue Microenvironment in Bladder Cancer using RNA Sequencing Data.

Purpose: Bladder cancer (BC) is one of the top 10 common tumors in the world. It has been reported that microbiota can colonize tissues and play important roles in tumorigenesis and progression. However, the current understanding of microorganisms in the BC tissue microenvironment remains unclear. Methods: In this study, we integrated the RNA-seq data of 479 BC tissue samples from seven datasets combined with a range of bioinformatics tools to explore the landscape of microbiome in the BC tissue microenvironment. Results: The pan-microbiome was estimated to surpass 1,400 genera. A total of seven core microbiota (Bacillus, Corynebacterium, Cutibacterium, Escherichia, Halomonas, Pasteurella, and Streptomyces) were identified. Among them, Bacillus was widely distributed in all datasets with a high relative abundance (10.11% of all samples on average). Moreover, some biological factors, including tissue source and tumor grade, were found significant effects on the microbial composition of the bladder tissue. Pseudomonas, Porphyrobacter, and Acinetobacter were enriched in tumor tissues, while Mycolicibacterium and Streptomyces were enriched in patients who showed durable response to BCG therapy. In addition, we established microbial co-occurrence networks and found that the BCG therapy may attenuate the microbiological interactions. Conclusions: This study clearly provided a microbial landscape of the BC tissue microenvironment, which was important for exploring the interactions between microorganisms and BC tissues. The identified specific taxa might be potential biomarkers for BC.

HES4 is a potential biomarker for bladder cancer: a Mendelian randomization study.

Background: Patients with bladder cancer (BLCA) have a poor prognosis and little progress has been made in treatment. Therefore, the purpose of this work was to employ Mendelian randomization (MR) and transcriptome analysis to identify a novel biomarker that could be used to reliably diagnose BLCA. Methods: TCGA-BLCA and GSE121711 datasets were obtained from public databases. Genome-wide association study (GWAS) data of BLCA outcome (373,295 samples containing 9,904,926 single nucleotide polymorphisms) were obtained through the IEU OpenGWAS database. Differentially expressed genes were applied as exposure factors, and MR analysis was performed to identify genes that had a causal relationship with BLCA. Then, the patients were divided into high and low expression groups according to the expression levels of candidate genes, and genes with survival differences were identified. Univariate and multivariate Cox regression were used to investigate the prognostic value of the expression of these genes. A nomogram was constructed based on independent prognostic factors, and we analyzed the functions and pathways associated with the identified genes as well as their relationship with the immune microenvironment. Results: HES4 was identified as a biomarker. HES4 status, age, and stage were identified as independent prognostic factors, and an excellent nomogram was established. Bioinformatic analysis suggested that HES4 might be associated with the activation of the immune response, bone development, and cancer pathways. The BLCA samples were divided into high and low HES4 groups. The stromal score and 33 immune cells were remarkably different between the two groups, with HES4 expression being negatively correlated with macrophages and mast cells, and positively correlated with eosinophils and central memory CD4+ T cells. Finally, HES4 was up-regulated in cancer samples in both TCGA-BLCA and GSE121711 datasets. Conclusion: This study identified HES4 as an independent prognostic factor for BLCA outcome based on MR and transcriptome analysis, which provides useful information for future research on and treatment of BLCA.

The value of ATAD3A as a potential biomarker for bladder cancer.

Bladder cancer (BCa) is a highly malignant tumor, and if left untreated, it can develop severe hematuria and tumor metastasis, thereby endangering the patient's life. The purpose of this paper was to detect the expression of ATAD3A in BCa and research the relationship between ATAD3A and pathological features of bladder cancer and the prognosis of patients. First, the expression of ATAD3A in BCa and normal bladder tissues was analyzed based on the UALCAN and Oncomine public databases. Second, 491 cases of surgically resected bladder cancer specimens and 110 cases of normal adjacent tissues were immunohistochemically stained. The expression of ATAD3A was quantified, and the value and prognosis of ATAD3A as a biomarker of BCa were evaluated. The expression of ATAD3A in bladder cancer tissues was higher than that in normal bladder mucosa. High expression of ATAD3A was correlated with patient age, tumor size, number of tumors, distant metastasis, lymph node metastasis, lymphovascular invasion, and TNM stage (p < 0.05). Overexpression of ATAD3A is closely related to cancer patient survival. The mean survival time of bladder cancer patients with high ATAD3A expression was shorter than those with low ATAD3A levels. According to the relative comparing result, the high ATAD3A expression herald reduced overall survival in BCa patients. The abnormal overexpression of ATAD3A may be related to the initiation and progress of bladder cancer. The upregulation of ATAD3A can be used as an effective indicator to diagnose bladder cancer and predict tumor progression. Furthermore, the combination of information from public databases and the results of clinical sample analysis can help us better understand the mechanism of action of molecular oncogenes in bladder cancer.

ZEB1-mediated biogenesis of circNIPBL sustains the metastasis of bladder cancer via Wnt/β-catenin pathway

BackgroundCircular RNAs (circRNAs) circularized by back-splicing of pre-mRNA are widely expressed and affected the proliferation, invasion and metastasis of bladder cancer (BCa). However, the mechanism underlying circRNA biogenesis in mediating the distant metastasis of BCa still unexplored.MethodsRNA sequencing data between BCa and normal adjacent tissues was applied to identify the differentially expressed circRNAs. The functions of circNIPBL in BCa were investigated via a series of biochemical experiments. The Clinical significance of circNIPBL was examined in a cohort of larger BCa tissues.ResultsIn the present study, we identified a novel circRNA (hsa_circ_0001472), circNIPBL, which was significantly upregulated and had great influence on the poor prognosis of patients with BCa. Functionally, circNIPBL promotes BCa metastasis in vitro and in vivo. Mechanistically, circNIPBL upregulate the expression of Wnt5a and activated the Wnt/β-catenin signaling pathway via directly sponged miR-16-2-3p, leading to the upregulation of ZEB1, which triggers the EMT of BCa. Moreover, we revealed that ZEB1 interacted with the flanking introns of exons 2–9 on NIPBL pre-mRNA to trigger circNIPBL biogenesis, thus forming a positive feedback loop. Importantly, circNIPBL overexpression significantly facilitated the distant metastasis of BCa in the orthotopic bladder cancer model, while silencing ZEB1 remarkably blocked the effects of metastasis induced by circNIPBL overexpression.ConclusionsOur study highlights that circNIPBL-induced Wnt signaling pathway activation triggers ZEB1-mediated circNIPBL biogenesis, which forms a positive feedback loop via the circNIPBL/miR-16-2-3p/Wnt5a/ZEB1 axis, supporting circNIPBL as a novel therapeutic target and potential biomarker for BCa patients.Graphical

Extracellular Vesicles as Potential Bladder Cancer Biomarkers: Take It or Leave It?

Bladder cancer (BC) is the 10th most frequently diagnosed cancer worldwide. Although urine cytology and cystoscopy are current standards for BC diagnosis, both have limited sensitivity to detect low-grade and small tumors. Moreover, effective prognostic biomarkers are lacking. Extracellular vesicles (EVs) are lipidic particles that contain nucleic acids, proteins, and metabolites, which are released by cells into the extracellular space, being crucial effectors in intercellular communication. These particles have emerged as potential tools carrying biomarkers for either diagnosis or prognosis in liquid biopsies namely urine, plasma, and serum. Herein, we review the potential of liquid biopsies EVs' cargo as BC diagnosis and prognosis biomarkers. Additionally, we address the emerging advantages and downsides of using EVs within this framework.

Transcription factor EB regulates phosphatidylinositol-3-phosphate levels that control lysosome positioning in the bladder cancer model

Lysosomes orchestrate degradation and recycling of exogenous and endogenous material thus controlling cellular homeostasis. Little is known how this organelle changes during cancer. Here we investigate the intracellular landscape of lysosomes in a cellular model of bladder cancer. Employing standardized cell culture on micropatterns we identify a phenotype of peripheral lysosome positioning prevailing in bladder cancer cell lines but not normal urothelium. We show that lysosome positioning is controlled by phosphatidylinositol-3-phosphate (PtdIns3P) levels on endomembranes which recruit FYVE-domain containing proteins for lysosomal dispersion. We identify transcription factor EB (TFEB) as an upstream regulator of PtdIns3P production by VPS34 that is activated in aggressive bladder cancer cells with peripheral lysosomes. This conceptually clarifies the dual role of TFEB as regulator of endosomal maturation and autophagy, two distinct processes controlled by PtdIns3P. Altogether, our findings uncover peripheral lysosome positioning, resulting from PtdIns3P production downstream of TFEB activation, as a potential biomarker for bladder cancer.

Six potential biomarkers for bladder cancer: key proteins in cell-cycle division and apoptosis pathways

BackgroundThe bladder cancer (BC) pathology is caused by both exogenous environmental and endogenous molecular factors. Several genes have been implicated, but the molecular pathogenesis of BC and its subtypes remains debatable. The bioinformatic analysis evaluates high numbers of proteins in a single study, increasing the opportunity to identify possible biomarkers for disorders.MethodsThe aim of this study is to identify biomarkers for the identification of BC using several bioinformatic analytical tools and methods. BC and normal samples were compared for each probeset with T test in GSE13507 and GSE37817 datasets, and statistical probesets were verified with GSE52519 and E-MTAB-1940 datasets. Differential gene expression, hierarchical clustering, gene ontology enrichment analysis, and heuristic online phenotype prediction algorithm methods were utilized. Statistically significant proteins were assessed in the Human Protein Atlas database. GSE13507 (6271 probesets) and GSE37817 (3267 probesets) data were significant after the extraction of probesets without gene annotation information. Common probesets in both datasets (2888) were further narrowed by analyzing the first 100 upregulated and downregulated probesets in BC samples.ResultsAmong the total 400 probesets, 68 were significant for both datasets with similar fold-change values (Pearson r: 0.995). Protein-protein interaction networks demonstrated strong interactions between CCNB1, BUB1B, and AURKB. The HPA database revealed similar protein expression levels for CKAP2L, AURKB, APIP, and LGALS3 both for BC and control samples.ConclusionThis study disclosed six candidate biomarkers for the early diagnosis of BC. It is suggested that these candidate proteins be investigated in a wet lab to identify their functions in BC pathology and possible treatment approaches.

Prioritizing potential circRNA biomarkers for bladder cancer and bladder urothelial cancer based on an ensemble model

Bladder cancer is the most common cancer of the urinary system. Bladder urothelial cancer accounts for 90% of bladder cancer. These two cancers have high morbidity and mortality rates worldwide. The identification of biomarkers for bladder cancer and bladder urothelial cancer helps in their diagnosis and treatment. circRNAs are considered oncogenes or tumor suppressors in cancers, and they play important roles in the occurrence and development of cancers. In this manuscript, we developed an Ensemble model, CDA-EnRWLRLS, to predict circRNA-Disease Associations (CDA) combining Random Walk with restart and Laplacian Regularized Least Squares, and further screen potential biomarkers for bladder cancer and bladder urothelial cancer. First, we compute disease similarity by combining the semantic similarity and association profile similarity of diseases and circRNA similarity by combining the functional similarity and association profile similarity of circRNAs. Second, we score each circRNA-disease pair by random walk with restart and Laplacian regularized least squares, respectively. Third, circRNA-disease association scores from these models are integrated to obtain the final CDAs by the soft voting approach. Finally, we use CDA-EnRWLRLS to screen potential circRNA biomarkers for bladder cancer and bladder urothelial cancer. CDA-EnRWLRLS is compared to three classical CDA prediction methods (CD-LNLP, DWNN-RLS, and KATZHCDA) and two individual models (CDA-RWR and CDA-LRLS), and obtains better AUC of 0.8654. We predict that circHIPK3 has the highest association with bladder cancer and may be its potential biomarker. In addition, circSMARCA5 has the highest association with bladder urothelial cancer and may be its possible biomarker.

Alpha-2-macroglobulin as a novel diagnostic biomarker for human bladder cancer in urinary extracellular vesicles.

Extracellular vesicles (EVs) derived from urine are promising tools for the diagnosis of urogenital cancers. Urinary EVs (uEVs) are considered potential biomarkers for bladder cancer (BC) because urine is in direct contact with the BC tumor microenvironment and thus reflects the current state of the disease. However, challenges associated with the effective isolation and analysis of uEVs complicate the clinical detection of uEV-associated protein biomarkers. Herein, we identified uEV-derived alpha-2-macroglobulin (a2M) as a novel diagnostic biomarker for BC through comparative analysis of uEVs obtained from patients with BC pre- and post-operation using an antibody array. Furthermore, enzyme-linked immunosorbent assay of uEVs isolated from patients with BC (n=60) and non-cancer control subjects (n=23) validated the significant upregulation of a2M expression in patient uEVs (p<0.0001). There was no significant difference in whole urine a2M levels between patients with BC and controls (p=0.317). We observed that compared to classical differential centrifugation, ExoDisc, a centrifugal microfluidic tangential flow filtration device, was a significantly more effective separation method for uEV protein analysis. We expect that our approach for EV analysis will provide an efficient route for the identification of clinically meaningful uEV-based biomarkers for cancer diagnosis.

Single-Domain Antibodies Used to Pretreat the Human Urinary Proteome in Cancer Biomarker Testing

A number of single-domain antibodies (nanobodies) obtained previously to major marker blood proteins were tested as tools to preprocess urine samples from patients with bladder cancer. Nanobody-based tools demonstrated unique possibilities for noninvasive diagnostic studies along with other conventional methods, such as electrophoresis and, in prospect, mass spectrometric analysis. A testing of 22 samples from bladder cancer patients showed that the development of bladder cancer is accompanied by an increase in the urine contents of major blood proteins, including those known as potential bladder cancer biomarkers. New nanobody-based immunosorbents allow both specific enrichment and specific removal of particular antigenic proteins and subproteomes associated with them from a biological fluid. The isolation of immune complexes from the urine of a particular patient is of particular interest. An initial study of the complexes showed not only increased contents of IgA and IgG at advanced stages of the disease, but also many other components, which provide potential biomarkers of the pathological process in a particular patient. It is intended to use the approaches proposed in this work in a future larger-scale study of urine samples from patients with bladder cancer at different stages of the disease in order to identify new promising biomarkers of bladder cancer.

Identification of Prognostic Biomarkers for Bladder Cancer Based on DNA Methylation Profile.

Background: DNA methylation is an important epigenetic modification, which plays an important role in regulating gene expression at the transcriptional level. In tumor research, it has been found that the change of DNA methylation leads to the abnormality of gene structure and function, which can provide early warning for tumorigenesis. Our study aims to explore the relationship between the occurrence and development of tumor and the level of DNA methylation. Moreover, this study will provide a set of prognostic biomarkers, which can more accurately predict the survival and health of patients after treatment. Methods: Datasets of bladder cancer patients and control samples were collected from TCGA database, differential analysis was employed to obtain genes with differential DNA methylation levels between tumor samples and normal samples. Then the protein-protein interaction network was constructed, and the potential tumor markers were further obtained by extracting Hub genes from subnet. Cox proportional hazard regression model and survival analysis were used to construct the prognostic model and screen out the prognostic markers of bladder cancer, so as to provide reference for tumor prognosis monitoring and improvement of treatment plan. Results: In this study, we found that DNA methylation was indeed related with the occurrence of bladder cancer. Genes with differential DNA methylation could serve as potential biomarkers for bladder cancer. Through univariate and multivariate Cox proportional hazard regression analysis, we concluded that FASLG and PRKCZ can be used as prognostic biomarkers for bladder cancer. Patients can be classified into high or low risk group by using this two-gene prognostic model. By detecting the methylation status of these genes, we can evaluate the survival of patients. Conclusion: The analysis in our study indicates that the methylation status of tumor-related genes can be used as prognostic biomarkers of bladder cancer.

Integrative Analysis Identified MCT4 as an Independent Prognostic Factor for Bladder Cancer.

BackgroundBladder cancer is the 10th most common cancer and most common urothelial malignancy worldwide. Prognostic biomarkers for bladder cancer patients are required for individualized treatment. Monocarboxylate transporter 4 (MCT4), encoded by SLC16A3 gene, is a potential biomarker for bladder cancer because of its crucial role in the lactate efflux in the aerobic glycolysis process. We aimed to study the association between MCT4 expression and the overall survival (OS) of bladder cancer patients.MethodsThe published single-cell RNA sequencing data of 49,869 bladder cancer cells and 15,827 normal bladder mucosa cells and The Cancer Genome Atlas (TCGA) bladder cancer cohort data were used to explore the mRNA expression of SLC16A3 in bladder cancer. Eighty-nine consecutive bladder cancer patients who had undergone radical cystectomy were enrolled as a validation cohort. The expression of MCT4 proteins in bladder cancer specimens was detected using immunohistochemistry staining. The Kaplan–Meier survival analysis and Cox regression were performed to analyze the association between MCT4 protein expression and OS in bladder cancer patients.ResultsSLC16A3 mRNA was upregulated in bladder cancer cells. The upregulated genes in SLC16A3-positive epithelial cells were enriched in the glycolysis process pathway and monocarboxylic acid metabolic process pathway. Patients with high SLC16A3 mRNA expression showed significantly poor OS (p = 0.016). High MCT4 protein expression was also found to be an independent predictor for poor OS in bladder cancer patients (HR: 2.462; 95% CI: 1.202~5.042, p = 0.014). A nomogram was built based on the results of the multivariate Cox analysis.ConclusionBladder cancer with high SLC16A3 mRNA expression has a poor OS. High MCT4 protein expression is an independent prognostic factor for bladder cancer patients who had undergone radical cystectomy.

Circulating Cell-Free DNA in Liquid Biopsies as Potential Biomarker for Bladder Cancer: A Systematic Review.

Simple SummaryBladder cancer (BC) is one of the most frequent cancers in the world and the urological tumor that presents the highest mortality. The diagnostic and prognostic methods available at present for BC are expensive and highly invasive for the patient, so the pursue of biomarkers that may replace those methods has been ongoing for years with limited success. One of these potential biomarkers is cell-free DNA, which can be found in liquid biopsies such as urine and blood. The present review summarizes the most recent research findings in the study of cell-free DNA to diagnose BC and even monitor treatment.Bladder cancer (BC) is among the most frequent cancer types in the world and is the most lethal urological malignancy. Presently, diagnostic and follow-up methods for BC are expensive and invasive. Thus, the identification of novel predictive biomarkers for diagnosis, progression, and prognosis of BC is of paramount importance. To date, several studies have evidenced that cell-free DNA (cfDNA) found in liquid biopsies such as blood and urine may play a role in the particular scenario of urologic tumors, and its analysis may improve BC diagnosis report about cancer progression or even evaluate the effectiveness of a specific treatment or anticipate whether a treatment would be useful for a specific patient depending on the tumor characteristics. In the present review, we have summarized the up-to-date studies evaluating the value of cfDNA as potential diagnostic, prognostic, or monitoring biomarker for BC in several biofluids.

The Roles of Glycans in Bladder Cancer.

Bladder cancer is one of the most common malignant tumors of the urogenital system with high morbidity and mortality worldwide. Early diagnosis and personalized treatment are the keys to successful bladder cancer treatment. Due to high postoperative recurrence rates and poor prognosis, it is urgent to find suitable therapeutic targets and biomarkers. Glycans are one of the four biological macromolecules in the cells of an organism, along with proteins, nucleic acids, and lipids. Glycans play important roles in nascent peptide chain folding, protein processing, and translation, cell-to-cell adhesion, receptor-ligand recognition, and binding and cell signaling. Glycans are mainly divided into N-glycans, O-glycans, proteoglycans, and glycosphingolipids. The focus of this review is the discussion of glycans related to bladder cancer. Additionally, this review also addresses the clinical value of glycans in the diagnosis and treatment of bladder cancer. Abnormal glycans are likely to be potential biomarkers for bladder cancer.

Effect of epigenetic imprinting biomarkers in urine exfoliated cells (UEC) on the diagnostic accuracy of low-grade bladder cancer.

e17027 Background: Urine Exfoliated Cells (UEC) is the most widely used sample for noninvasive bladder cancer detection. However, current UEC-based methods including urinary cytology and other molecular detections showed low sensitivities especially for low-grade cancer (&lt; 50% sensitivity). Epigenetic alterations such as elevated allelic expression of imprinted genes usually occur at early stages of malignancy, and can be considered as potential bladder cancer biomarkers. In this study, Quantitative Chromogenic Imprinting Gene In-Situ Hybridization (QCIGISH) was conducted to analyze the biallelic expression (BAE) and multiallelic expression (MAE) in UEC, and develop a more accurate method for early stage bladder cancer. Methods: 53 patients with urinary system diseases including 13 low-grade bladder cancer, 24 high-grade bladder cancer and 16 benign lesions, as well as 28 healthy volunteers were recruited in clinical trial NCT03563443 for validation. The total expression (TE), BAE and MAE of imprinted genes GNAS, PEG10, GRB10, SNRPN and HM13 were blindly detected by QCIGISH. The severity of malignancy was predicted by a grading model previously established on 229 tissue FFPE and cystoscopic biopsy samples, and subsequently validated with the pathology and clinical diagnosis results. Results: The QCIGISH method achieved 84.6% and 95.8% sensitivities for low- and high-grade bladder cancers, respectively, with an equally high specificity of 97.7%. The sensitivity of QCIGISH for low-grade bladder cancer is much higher than standard urinary cytology (16%), and FDA-approved molecular tests such as Hemoglobin Dipstick (38%), BTA Stat (36%), NMP22 BladderChek (25%), and ImmunoCyt (47%). Conclusions: The high accuracy of QCIGISH especially for low-grade bladder cancer demonstrated its great potential in becoming an important and powerful clinical tool for noninvasive diagnosis and large-scale screening for early bladder cancer.

Evaluation of ASPM and TEF Gene Expressions as Potential Biomarkers for Bladder Cancer.

Bladder cancer is one of the most predominant tumors of the genitourinary tract. In addition to pathological findings, the molecular modifications that might affect tumorigenesis and tumor outcome should be considered when treating bladder cancer. Accordingly, we aimed to investigate the expression levels of both the ASPM and TEF genes in bladder cancer tissues and their value in disease prognosis. The expression levels of the ASPM and TEF genes were analyzed by quantitative real-time PCR (qRT-PCR) in 90 bladder cancer tissue specimens and 90 specimens of normal urinary bladder tissue taken away from the tumor site. The upregulation of ASPM expression and the downregulation of TEF expression were observed in bladder cancer tissues compared to adjacent normal tissues, and these levels were correlated with high-grade tumors, advanced stage disease and the presence of metastasis. Both genes had the ability to predict metastatic association with sensitivity (84.62%) and specificity (68.42%; *P < 0.001) for the ASPM gene and for the TEF gene with sensitivity (80.77%) and specificity (78.95%; *P < 0.001). Additionally, Kaplan-Meier survival analysis indicated that elevated ASPM expression levels and reduced TEF expression levels significantly correlated with decreased overall survival and progression-free survival. The current analysis concludes that ASPM and TEF expressions might be used as potential biomarkers in bladder cancer patients.

Long Noncoding RNA MNX1 antisense RNA 1 Exerts Oncogenic Functions in Bladder Cancer by Regulating miR-218-5p/RAB1A Axis.

LncRNA MNX1 antisense RNA 1 (MNX1-AS1) is significantly overexpressed in patients with bladder cancer, suggesting that it might be associated with bladder cancer. However, the molecular mechanism of MNX1-AS1 in bladder cancer remained indistinct. To illustrate the role of MNX1-AS1 in bladder cancer, the gain- and loss-of-function experiments were conducted in bladder cancer cells. Reduced expression of MNX1-AS1 could suppress cell proliferation, migration, invasion, and epithelial-mesenchymal transition in bladder cancer cells, whereas overexpression of MNX1-AS1 resulted in the opposite effects. Mechanistic analysis demonstrated that miR-218-5p was a direct target of RAB1A. MNX1-AS1 could competitively bind to miR-218-5p to regulate RAB1A expression in bladder cancer cells. Furthermore, in vivo experiments revealed that reduced expression of MNX1-AS1 inhibited tumor growth and metastasis. Taken together, MNX1-AS1 functions as a sponge to miR-218-5p to modulate RAB1A expression in bladder cancer, which suggests that MNX1-AS1 might serve as a novel therapeutic target and a novel biomarker for metastasis and prognosis in bladder cancer. SIGNIFICANCE STATEMENT: Our study demonstrates that long noncoding RNA MNX1-AS1 promotes the initiation and progression of bladder cancer. MNX1-AS1 regulates RAB1A expression to promote proliferation, migration, invasion, and epithelial-mesenchymal transitions of bladder cancer cells via miR-218-5p, which contributes to the tumor growth and metastasis of bladder cancer. Collectively, these results suggest that MNX1-AS1 might serve as a potential biomarker for bladder cancer.