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Objective: To explore genes related to costimulatory molecule related to the prognosis of bladder cancer, and to construct and evaluate prognosis model based on costimulatory molecule-based signature (CMS). Methods: Gene expression matrix and clinical information of bladder cancer patients were downloaded from TCGA database and GEO database (GSE31684), and costimulatory molecule-related genes were retrieved from the literature. The univariate and multivariate Cox analysis were used to screened prognostic-related genes and constructed prognostic model. Forecast accuracy of model was verified in TCGA training group, TCGA validation data group and GEO group by Kaplan-Meier survival analysis and receiver operating characteristic curve (ROC). Considering risk score and clinical characteristics, we constructed a nomogram and evaluated its performance by consistency analysis and ROC. CIBERSORT algorithm was used to analyze immune cell composition of tumor microenvironment infiltration, and gene set enrichment analysis (GSEA) was performed to explore the potential mechanism. Results: Four prognostic-related CMSs were found: TNFRSF14, CD276, ICOS and TMIGD2, of which three were included in the risk score construction. Multivariate Cox regression results showed that the risk score based on CMS was an independent prognostic factor for bladder cancer patients. Consistency analysis and ROC results showed that the nomogram had ideal prognosis prediction accuracy. Immune infiltration analysis showed that the high risk group was likely to be in immunosuppressive state. GSEA results suggested that genes in high risk group were enriched in extracellular matrix (ECM) receptors interaction, cell cycle and other pathways. Conclusion:TNFRSF14, CD276 and ICOS may be potential prognostic biomarkers for bladder cancer patients. CMS-based risk score and nomogram could contribute to early prognosis and choice of personalized treatment. [ABSTRACT FROM AUTHOR]

Bladder cancer (BLCA) is a common and difficult‐to‐manage disease worldwide. Most common type of BLCA is urothelial carcinoma (UC). Fibrillin 2 (FBN2) was first discovered while studying Marfan syndrome, and its encoded products are associated with elastin fibres. To date, the role of FBN2 in BLCA remains unclear. The authors first downloaded data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). The patients were divided into high FBN2 expression and low FBN2 expression groups, and the survival curve, clinical characteristics, tumour microenvironment (TME), and immune cell differences were analysed between the two groups. Then, the differentially expressed genes (DEGs) were filtered, and functional enrichment for DEGs was performed. Finally, chemotherapy drug susceptibility analysis based on the high and low FBN2 groups was conducted. The authors found upregulated expression of FBN2 in BLCA and proved that FBN2 could be an independent prognostic factor for BLCA. TME analysis showed that the expression of FBN2 affects several aspects of the TME. The upregulated expression of FBN2 was associated with a high stromal score, which may lead to immunosuppression and be detrimental to immunotherapy. In addition, the authors found that NK cells resting, macrophage M0 infiltration, and other phenomena of immune cell infiltration appeared in the high expression group of FBN2. The high expression of FBN2 was related to the high sensitivity of some chemotherapy drugs. The authors systematically investigated the effects and mechanisms of FBN2 on BLCA and provided a new understanding of the role of FBN2 as a risk factor and TME influencer in BLCA. [ABSTRACT FROM AUTHOR]

Objective. Bladder cancer (BC) is the most common malignancy in the urinary system and is prone to recurrence and metastasis. Pyroptosis is a kind of cell necrosis that is triggered by the gasdermin protein family. lncRNAs are noncoding RNAs that are more than 200 nucleotides long. Both pyroptosis and lncRNAs are associated with tumor development and progression. This study is aimed at exploring and establishing a prognostic signature of BC based on pyroptosis-related lncRNAs. Methods. In this study, The Cancer Genome Atlas (TCGA) database provided us with the RNA sequencing transcriptome data of bladder cancer patients, and we identified differentially expressed pyroptosis-related lncRNAs in bladder cancer. Then, the prognostic significance of these lncRNAs was assessed using univariate Cox regression analysis and LASSO regression analysis. Subsequently, 4 pyroptosis-related lncRNAs, namely, AL121652.1, AL161729.4, AC007128.1, and AC124312.3, were identified by multivariate Cox regression analysis, thus constructing the prognostic risk model. Then, we compared the levels of immune infiltration, differences in cell function, immune checkpoints, and m6A-related gene expression levels between the high- and low-risk groups. Result. Patients were divided into low-risk or high-risk groups based on the median risk score. Kaplan–Meier survival analysis indicated that the overall survival of bladder cancer patients in the low-risk group was substantially superior to that in the high-risk group (p < 0.001). The receiver operating characteristic (ROC) curve further confirmed the credibility of our model. Moreover, gene set enrichment analysis (GSEA) indicated that these were different signal pathways significantly enriched between the two groups. Immune infiltration, immune checkpoint, and N6-methyladenosine-related gene analysis also reflected that there were notable differences between the two groups. Conclusion. Therefore, this prognostic risk model is based on the level of pyroptotic lncRNAs, which is conducive to individualized assessment of the risk of patients and provides a reference for clinical treatment. This will also help provide insights into the prognosis and treatment of bladder cancer. [ABSTRACT FROM AUTHOR]

To predict survival outcomes for individual patients with clinical T1 high-grade (T1HG) bladder cancer (BC), data from the Surveillance Epidemiology and End Results (SEER) database were analyzed in the present study. The data of 6,980 cases of T1HG BC between 2004 and 2014 were obtained from the SEER database. Uni- and multivariate Cox analyses were performed to identify significant prognostic factors. Subsequently, prognostic nomograms for predicting 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates were constructed based on the SEER database. Clinical information from the SEER database was divided into internal and external groups and used to validate the nomograms. In addition, calibration plot diagrams and concordance indices (C-indices) were used to verify the predictive performance of the nomogram. A total of 6,980 patients were randomly allocated to the training cohort (n=4,886) or the validation cohort (n=2094). Univariate and multivariate Cox analyses indicated that age, ethnicity, tumor size, marital status, radiation and surgical status were independent prognostic factors. These characteristics were used to establish nomograms. The C-indices for OS and CSS rate predictions for the training cohort were 0.707 (95% CI, 0.693–0.721) and 0.700 (95% CI, 0.679–0.721), respectively. Internal and external calibration plot diagrams exhibited an excellent consistency between actual survival rates and nomogram predictions, particularly for 3- and 5-year OS and CSS. The significant prognostic factors in patients with T1HG BC were age, ethnicity, marital status, tumor size, status of surgery and use of radiation. In the present study, a nomogram was developed that may serve as an effective and convenient evaluation tool to help surgeons perform individualized survival evaluations and mortality risk determination for patients with T1HG BC. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to identify key genes and investigate the related molecular mechanisms of bladder cancer (BC) progression. From the Gene Expression Omnibus database, the gene expression dataset GSE7476 was downloaded, which contained 43 BC samples and 12 normal bladder tissues. GSE7476 was analyzed to screen the differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for the DEGs using the DAVID database, and a protein‑protein interaction (PPI) network was then constructed using Cytoscape software. The results of the GO analysis showed that the upregulated DEGs were significantly enriched in cell division, nucleoplasm and protein binding, while the downregulated DEGs were significantly enriched in ‘extracellular matrix organization’, ‘proteinaceous extracellular matrix’ and ‘heparin binding’. The results of the KEGG pathway analysis showed that the upregulated DEGs were significantly enriched in the ‘cell cycle’, whereas the downregulated DEGs were significantly enriched in ‘complement and coagulation cascades’. JUN, cyclin‑dependent kinase 1, FOS, PCNA, TOP2A, CCND1 and CDH1 were found to be hub genes in the PPI network. Sub‑networks revealed that these gene were enriched in significant pathways, including the ‘cell cycle’ signaling pathway and ‘PI3K‑Akt signaling pathway’. In summary, the present study identified DEGs and key target genes in the progression of BC, providing potential molecular targets and diagnostic biomarkers for the treatment of BC. [ABSTRACT FROM AUTHOR]