Identification of Biomarkers Related to Prognosis of Bladder Transitional Cell Carcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Liu Z
PROVIDER: S-EPMC8381732 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundAimed to facilitate candidate biomarkers selection and improve network-based multi-target therapy, we perform comparative proteomics research on muscle-invasive bladder transitional cell carcinoma. Laser capture microdissection was used to harvest purified muscle-invasive bladder cancer cells and normal urothelial cells from 4 paired samples. Two-dimensional liquid chromatography tandem mass spectrometry was used to identify the proteome expression profile. The differential proteins were further analyzed using bioinformatics tools and compared with the published literature.ResultsA total of 885/890 proteins commonly appeared in 4 paired samples. 295/337 of the 488/493 proteins that specific expressed in tumor/normal cells own gene ontology (GO) cellular component annotation. Compared with the entire list of the international protein index (IPI), there are 42/45 GO terms exhibited as enriched and 9/5 exhibited as depleted, respectively. Several pathways exhibit significantly changes between cancer and normal cells, mainly including spliceosome, endocytosis, oxidative phosphorylation, etc. Finally, descriptive statistics show that the PI Distribution of candidate biomarkers have certain regularity.ConclusionsThe present study identified the proteome expression profile of muscle-invasive bladder cancer cells and normal urothelial cells, providing information for subcellular pattern research of cancer and offer candidate proteins for biomarker panel and network-based multi-target therapy.
| S-EPMC3118115 | biostudies-literature
Project description:MicroRNA (miRNA) are short nucleotide strands with a regulatory function in the cell. Several miRNAs have been shown to be useful as biomarkers for different neoplasms. The aim of this project was to assess whether levels of miRNA in cell free urine could be used as a biomarker in transitional cell carcinoma (TCC).cDNA libraries were produced based on small RNAs in urine samples of fourteen TCC patients and twenty healthy volunteers. Resulting reads were deep sequenced on Illumina HiSeq sequencer with the intent of characterizing cell free urine miRNA profiles. A statistically significant difference was found for a single miRNA; miR-210 was > sixfold higher in the TCC group compared to the control group. Furthermore, we were able to produce a diagnostic score by summing of standardized levels of overexpressed miRNA. This score was considerably higher in TCC patients with a sensitivity of 0.93, specificity of 0.76 and negative predictive value > 0.97.
| S-EPMC5708087 | biostudies-other
Project description:Transitional bladder carcinoma (BCa) is prevalent in developed countries, particularly among men. Given that these tumors frequently recur or progress, the early detection and subsequent monitoring of BCa at different stages is critical. Current BCa diagnostic biomarkers are not sufficiently sensitive for substituting or complementing invasive cystoscopy. Here, we sought to identify a robust set of urine biomarkers for BCa detection. Using a high-resolution, mass spectrometry-based, quantitative proteomics approach, we measured, compared and validated protein variations in 451 voided urine samples from healthy subjects, non-bladder cancer patients and patients with non-invasive and invasive BCa. We identified five robust biomarkers: Coronin-1A, Apolipoprotein A4, Semenogelin-2, Gamma synuclein and DJ-1/PARK7. In diagnosing Ta/T1 BCa, these biomarkers achieved an AUC of 0.92 and 0.98, respectively, using ELISA and western blot data (sensitivity, 79.2% and 93.9%; specificity, 100% and 96.7%, respectively). In diagnosing T2/T3 BCa, an AUC of 0.94 and 1.0 was attained (sensitivity, 86.4% and 100%; specificity, 100%) using the same methods. Thus, our multiplex biomarker panel offers unprecedented accuracy for the diagnosis of BCa patients and provides the prospect for a non-invasive way to detect bladder cancer.
| S-EPMC4537032 | biostudies-literature
Project description:ObjectiveTo determine if a human bladder cancer-specific peptide named PLZ4 can target canine bladder cancer cells.Experimental designThe binding of PLZ4 to five established canine invasive transitional cell carcinoma (TCC) cell lines and to normal canine bladder urothelial cells was determined using the whole cell binding assay and an affinitofluorescence assay. The WST-8 assay was performed to determine whether PLZ4 affected cell viability. In vivo tumor-specific homing/targeting property and biodistribution of PLZ4 was performed in a mouse xenograft model via tail vein injection and was confirmed with ex vivo imaging.ResultsPLZ4 exhibited high affinity and specific dose-dependent binding to canine bladder TCC cell lines, but not to normal canine urothelial cells. No significant changes in cell viability or proliferation were observed upon incubation with PLZ4. The in vivo and ex vivo optical imaging study showed that, when linked with the near-infrared fluorescent dye Cy5.5, PLZ4 substantially accumulated at the canine bladder cancer foci in the mouse xenograft model as compared to the control.Conclusions and clinical relevancePLZ4 can specifically bind to canine bladder cancer cells. This suggests that the preclinical studies of PLZ4 as a potential diagnostic and therapeutic agent can be performed in dogs with naturally occurring bladder cancer, and that PLZ4 can possibly be developed in the management of canine bladder cancer.
| S-EPMC3040722 | biostudies-literature
Project description:Bladder carcinoma is the fourth most common cancer in men and the eighth most common cancer among women. Our study is aimed to characterise tumour-associated antigen peptides of transitional cell carcinoma of the bladder (TCC). A DNA micro-array-based differential display analysis of 10 000 genes was carried out, and MAGE-A8 gene expression was detected in the tumour, and not in the normal bladder. High occurrence of MAGE-A8 expression was observed in fresh tumour samples (17 out of 23) and TCC lines (four of eight). The MAGE-A8 protein sequence was screened for HLA-A2.1-binding motifs, six potential peptides were synthesised, and peptides binding to HLA-A2.1 were assured. Immunogenicity and antigenicity of the MAGE-A8 peptides were examined in the HHD system, murine class I MHC knockout mice, transgenic for HLA-A2.1. The MAGE-A8 peptide immunogenicity was examined in three modes of vaccination, delivered intranasally with cholera toxin, injected into the tail base with complete Freund's adjuvant (CFA), or presented directly as loaded onto cell surface HLA-A2.1 molecules. Two peptides, 8.1 and 8.3, induce CTL that kills the T24 TCC line in vitro, and prime human lymphocyte response of healthy donors. These results demonstrate the potential use of the MAGE-A8 peptides for specific immunotherapy of TCC.
| S-EPMC2409814 | biostudies-literature
Project description:BackgroundThe Hedgehog (Hh) signalling pathway functions as an organiser in embryonic development. Recent studies have shown constitutive activation of this pathway in various malignancies, but its role in bladder cancer remains poorly studied.MethodsExpression levels of 31 genes and 9 microRNAs (miRNAs) involved in the Hh pathway were determined by quantitative real-time RT-PCR in 71 bladder tumour samples (21 muscle-invasive (MIBC) and 50 non-muscle-invasive (NMIBC) bladder cancers), as well as in 6 bladder cancer cell lines.ResultsThe SHH ligand gene and Gli-inducible target genes (FOXM1, IGF2, OSF2, H19, and SPP1) were overexpressed in tumour samples as compared with normal bladder tissue. SHH overexpression was found in 96% of NMIBC and 52% of MIBC samples, as well as in two bladder cancer cell lines. Altered expression of miRNAs supported their oncogene or tumour-suppressor gene status. In univariate analysis, high expression levels of PTCH2, miRNA-92A, miRNA-19A, and miRNA-20A were associated with poorer overall survival in MIBC (P=0.02, P=0.012, P=0.047, and P=0.036, respectively).ConclusionWe observed constitutive activation of the Hh pathway in most NMIBC and about 50% of MIBC. We also found that some protein-coding genes and miRNAs involved in the Hh pathway may have prognostic value at the individual level.
| S-EPMC3304423 | biostudies-literature
Project description:Bladder transitional cell carcinoma (BTCC) forms more than 90% of bladder cancer cases. It brings challenges to the early diagnosis and therapy of BTCC, due to lack of efficient screening biomarkers. We used weighted gene co-expression network analysis (WGCNA) combined competing endogenous RNA (ceRNA) network construction depending on TCGA datasets to investigate potential hub genes and regulatory pathways associated with occurrence and progression of BTCC. We further used real-time polymerase chain reaction (RT-PCR) to validate the relative expression genes correlated with BTCC. By WGCNA, the gene co-expression module with 11 genes was found corelated with BTCC tumour stage and prognosis after survival analyses. Ultimately, we put 100 highly stage-related genes into the above constructed ceRNA network and then constructed another new network. Among them, all elements in AC112721.1/LINC00473/AC128709.1-hsa-mir-195-RECK and LINC00460-hsa-mir-429-ZFPM2 axes were simultaneously corelated with overall survival. RT-PCR showed that AKAP12 was downregulated in tumour tissues. The hub genes screened out in the present study may provide ideals for further treatment on BTCC.
| S-EPMC10902574 | biostudies-literature
Project description:The H3K27me3 ChIP-seq data for the human bladder transitional cell carcinoma cell line CL1207 were generated in order to detect regions of regional epigenetic silencing in this cell line and test the performance of several peak calling tools: CCAT (Xu et al., 2010) and HMCan (Ashoor et al., "HMCan M-bM-^@M-^S a tool to detect chromatin modifications in cancer samples using ChIP-seq data", submitted). The human bladder cancer cell line CL1207 was derived from a muscle-invasive bladder cancer (De Boer et al., 1997). 5x105 cells were immunoprecipitated per ChIP assay with 4 M-NM-<g of rabbit polyclonal antibodies against trimethyl histone H3 lysine 27 (Upstate Biotechnology, Santa Cruz, CA) and DynabeadsM-BM-. Protein A (Invitrogen, Cergy Pontoise, France) in dilution buffer containing 1% Triton X-100, 150 mM NaCl, 2 mM EDTA, 20 mM TrisM-bM-^@M-^SHCl at pH 8.0, and protease inhibitors. Six ChIP assays in the same experimental conditions were necessary to perform one ChIP-Seq experiment, so the total of 3x106 cells for each of the duplicates.
2014-01-07 | E-GEOD-44438 | biostudies-arrayexpress
Project description:BackgroundPrevious studies have shown that RNA Polymerase III Subunit G (POLR3G) has oncogenic effects in cultured cells and mice. However, the role of POLR3G in transitional cell carcinoma (TCC) has not been reported. This study explores the potential of POLR3G as a novel molecular marker for TCC.MethodsThe RNA sequencing data and clinical information of patients with TCC were downloaded from The Cancer Genome Atlas official website. Transcriptome analysis was performed as implemented in the edgeR package to explore whether POLR3G was up-regulated in TCC tissues compared to normal bladder tissues. The expression of POLR3G in bladder cancer cell line T24 and human uroepithelial cell line SV-HUC-1 were detected via quantitative real time polymerase chain reaction (qRT-PCR). Correlations between POLR3G expression and clinicopathological characteristics were analyzed using Mann-Whitney U test or Kruskal-Wallis H test. Clinicopathological characteristics associated with overall survival were explored using the Kaplan-Meier method and Cox regression analyses. Gene set enrichment analysis (GSEA) was performed to explore the associated gene sets enriched in different POLR3G expression phenotypes and the online tool Tumor IMmune Estimation Resource (TIMER) was used to explore the correlation between POLR3G expression and tumor immune infiltration in TCC.ResultsTranscriptome analysis showed that POLR3G was significantly up-regulated in TCC tissues compared to normal bladder tissues. Furthermore, qRT-PCR revealed high expression of POLR3G in T24 cells compared to SV-HUC-1 cells. Overall, POLR3G expression was associated with race, tumor status, tumor subtype, T classification, and pathological stage. Kaplan-Meier survival analysis revealed that higher POLR3G expression was associated with lower overall survival. The univariate Cox regression model revealed that age at diagnosis, pathological stage, and POLR3G expression were associated with prognosis of TCC patients. Further multivariate analyses identified these three clinicopathological characteristics as independent prognostic factors for overall survival. GSEA analysis showed that several gene sets associated with tumor development and metastasis, including TGF-β signaling, PI3K-AKT-mTOR signaling, and IL6-JAK-STAT3 signaling, were significantly enriched in POLR3G high expression phenotype. Immune infiltration analysis revealed that the expression of POLR3G was significantly correlated with infiltrating levels of immune cells, including CD8+ T cells, neutrophils, and dendritic cells; and the expression of POLR3G was also significantly correlated with the expression of immune checkpoint molecules, such as PD1, PD-L1, PD-L2, CTLA4, LAG3, HAVCR2, and TIGIT.ConclusionsPOLR3G was up-regulated in TCC and high POLR3G expression correlated with poor prognosis. POLR3G can potentially be used as a prognostic marker for TCC and might be of great value in predicting the response to immunotherapy.
| S-EPMC7646299 | biostudies-literature
Project description:The H3K27me3 ChIP-seq data for the human bladder transitional cell carcinoma cell line CL1207 were generated in order to detect regions of regional epigenetic silencing in this cell line and test the performance of several peak calling tools: CCAT (Xu et al., 2010) and HMCan (Ashoor et al., "HMCan – a tool to detect chromatin modifications in cancer samples using ChIP-seq data", submitted).
2014-01-07 | GSE44438 | GEO