Molecular changes during progression from early stage to advanced urothelial carcinoma
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PROVIDER: PRJNA529496 | ENA |
REPOSITORIES: ENA
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Project description:It is unclear how urothelial carcinoma of the urinary bladder change, genetically and phenotypically, as patients progress from recurrent non muscle-invasive (NMI) to muscle-invasive (MI) disease or disease that require radical cystectomy. This data set contains gene expression data from 200 samples in a longitudinal study of such patients. Overlap with previously GEO-published cohorts from our lab is described in the metadata.
2020-01-20 | GSE128959 | GEO
Project description:Micro-RNA expression profiles in upper tract urothelial carcinoma differentiate stage and tumor progression
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Project description:Micro-RNA expression profiles in upper tract urothelial carcinoma differentiate stage and tumor progression: screening data
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Project description:To identify and evaluate the prognostic ability of progression-free survival-related profile for advanced-stage ovarian cancer, advanced-stage serous ovarian cancer tissues from 110 patients who received primary surgery and a platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays of more than 40,000 transcripts. We first selected 88 genes by a univariate Cox proportional hazard analysis (p<0.01) and next optimized regression coefficients by ridge regression model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66–5.43; p,0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20–1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008). In multivariable analysis, our prognostic index was independently associated with progression-free survival times compared to other clinical factors (p<0.001). Furthermore, the prognostic ability of our prognostic index was validated in external, publicly available dataset (n = 87), and was proved in multivariate analysis (p = 0.0032). These results suggest that disease progression or recurrence of advanced-stage serous ovarian cancer can be predicted by gene expression profile. The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer.
2010-03-22 | GSE17260 | GEO
Project description:Micro-RNA expression profiles in upper tract urothelial carcinoma differentiate stage and tumor progression: secondary data set
| PRJNA490640 | ENA
Project description:Even though urothelial cancer (UC) is the fourth common tumor type among males, progress in treatment development has been deficient. Pathological assessment provides the urologists with only a broad classification, complicated by frequent disagreement among pathologist and the co-existence of different grading systems. Consequently, there is a great need for an objective, reproducible and biologically relevant classification system to make treatment more efficient. In the present investigation we present a molecular taxonomy for UC stratification based on integrated genomics. We used gene expression profiles from 308 UC to define seven molecular subtypes using step-by-step partitions and a bootstrap approach. Results were validated in three independent and publically available data sets. The subtypes differ significantly with respect to expression of cell cycle genes, of receptor tyrosine kinases particularity FGFR3, ERBB2 (HER2), and EGFR, of an FGFR3 associated gene expression signature, of cytokaratins, and of cell adhesion genes. The subtypes also differ significantly with respect to FGFR3, PIK3CA, and TP53 mutations. The expression of key proteins was validated by IHC on TMA. A further inspection indicated that the subtypes could be reduced to four major types of UC; Urobasal/D-driven, Genomically unstable/E-driven, Evolved urobasal, and Basal/SCC like, with characteristic and highly divergent molecular phenotypes. We show that the molecular subtypes cut across pathological classification and that tumors classified as one subtype maintain their characteristic molecular phenotype irrespective of pathological stage and grade. Available data from the Drugbank database and the Cochrane central registry of controlled trials indicate that susceptibility to specific drugs is more likely to be associated with the molecular stratification than with pathological classification. The presented molecular taxonomy stratifies UC into subtypes with distinct molecular phenotypes and biological properties. We anticipate that the molecular taxonomy will be a useful tool in future clinical investigations. Total RNA from fresh-frozen resection samples of 308 urothelial carcinomas was hybridized to the Illumina HumanHT-12 V3.0 expression beadchip arrays (Illumina Inc) at the SCIBLU Genomics Centre at Lund University Sweden (http://www.lth.se/sciblu). Supplementary files: GSE32894_non-normalized_308UCsamples.txt file = Raw intensity values for 308 UC (urothelial tumor) samples subjected only to background correction. GSE32894_reps_normals_preprocess*.txt files = Descriptive details and non-normalized data for technical replicates and normal samples that were used only in the preprocessing of the data. This dataset partly overlaps with Series GSE32549. Names of the overlapping sample names are the same, but the title of each sample is unique to the hybridization.
2012-05-23 | E-GEOD-32894 | biostudies-arrayexpress
Project description:The long-term survival of advanced urothelial carcinoma (UCa) patients is limited due to an innate resistance to treatment. We identified elevated expression of the histone methyltransferase EZH2 as a hallmark of aggressive UCa, and therefore, hypothesized that EPZ-011989, a small molecule catalytic inhibitor of EZH2, might have anti-tumor effects in UCa. Here we show that in a carcinogen-induced mouse bladder cancer model, EZH2 inhibition results in reduced tumor progression, elevated tumor infiltrating T cells, increased pro-inflammatory cytokine secretion and MHC class II expression on UCa cells. Treatment of mice with EPZ011989 causes increased MHC class II expression on the urothelium, and was able to activate CD4+ T cells, which is completely abrogated with genetic ablation of the acquired immune system. These findings support a unique role for EZH2 catalytic activity in mediating UCa immune evasion and, for the first time, prove the efficacy of EZH2 catalytic inhibitors in a UCa model, a finding that can potentially be expanded to humans with UCa.
2022-08-15 | GSE209852 | GEO
Project description:The long-term survival of advanced urothelial carcinoma (UCa) patients is limited due to an innate resistance to treatment. We identified elevated expression of the histone methyltransferase EZH2 as a hallmark of aggressive UCa, and therefore, hypothesized that EPZ-011989, a small molecule catalytic inhibitor of EZH2, might have anti-tumor effects in UCa. Here we show that in a carcinogen-induced mouse bladder cancer model, EZH2 inhibition results in reduced tumor progression, elevated tumor infiltrating T cells, increased pro-inflammatory cytokine secretion and MHC class II expression on UCa cells. Treatment of mice with EPZ011989 causes increased MHC class II expression on the urothelium, and was able to activate CD4+ T cells, which is completely abrogated with genetic ablation of the acquired immune system. These findings support a unique role for EZH2 catalytic activity in mediating UCa immune evasion and, for the first time, prove the efficacy of EZH2 catalytic inhibitors in a UCa model, a finding that can potentially be expanded to humans with UCa.
2022-08-15 | GSE209851 | GEO
Project description:Abstract Background: Histone deacetylase (HDAC) inhibition has shown some efficacy in urothelial carcinoma (UC); the genomic basis for clinical response is not known. Methods: In two separate phase I clinical trials testing HDAC inhibitors in advanced solid tumors, we identified one patient with advanced UC who had a complete response (CR) to belinostat and one with advanced UC who had a partial response (PR) to panobinostat. The archived tumor of the responders was genomically characterized and studied in comparison to others with UC, in the context of their response to HDAC inhibition on trial. UC cell lines treated with panobinostat were studied to elucidate the mechanisms of benefit. Results: The two patients who responded to HDAC inhibition had ARID1A and FANCD2 mutations. The patient who had a CR to HDAC inhibition had the highest tumor mutational burden of all tumors. Corroborating the basis of sensitivity, transcriptional profiling of platinum resistant ARID1A mutated HT1197 cells treated with panobinostat revealed downregulation of cyto-proliferative and DNA repair gene sets and upregulation of inflammatory gene sets. Conclusions: Clinical efficacy of HDAC inhibition in UC may be dependent on overlapping SWI/SNF pathway mutations and DNA repair defects. Tumor mutational burden may predict the depth and duration of benefit.
2018-10-31 | GSE103928 | GEO
Project description:EZH2 Catalytic Inhibition Prevents Urothelial Carcinoma Progression Through Immune Activation.
| PRJNA862706 | ENA