Epigenome analysis of upper-tract urothelial carcinomas samples and normal adjacent tissue (NAT)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE161651 | GEO | 2020/11/30
REPOSITORIES: GEO
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Project description:Genome-wide methylation analysis of upper urinary tract urothelial carcinoma using Infinium MethylationEPIC BeadChip Kit
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Project description:Epigenome analysis of upper-tract urothelial carcinomas samples and normal adjacent tissue (NAT)
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Project description:Genome-wide copy number analysis of upper urinary tract urothelial carcinoma using GeneChip Human Mapping 250K Nspl
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Project description:Molecular profiles and urinary biomarkers of upper tract urothelial carcinomas associated with aristolochic acid exposure
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Project description:Accurate grading and staging of upper tract urothelial carcinoma (UTUC) often proves challenging, and improved knowledge of tumor biology could identify patients who are candidates for minimally invasive therapy rather than nephroureterectomy (NU). Total RNA was extracted from formalin-fixed, paraffin-embedded NU samples. Thirty-five samples with diverse pathologies were selected and screened via microRNA RT-qPCR array for 752 unique miRNA. Validation of differentially expressed miRNA was performed on 123 additional NU tissue specimens from two institutions. The data presented in this series are for the 35 samples analyzed in the screening analysis. The data was normalized to the global mean of each sample using microRNA detected in all samples with a Cq<37.
2019-01-01 | GSE119601 | GEO
Project description:Expression profiling by arrays Urothelial carcinoma (UC) can arise at any location along the urothelial tract, including the urethra, bladder, ureter or renal pelvis. Although tumors arising in these various locations demonstrate similar morphology, it is unclear whether the gene expression profiles are similar in the upper tract (ureter and renal pelvis) or in the lower tract (bladder and urethra) carcinomas, especially given their different embryologic origins. As differences may facilitate potentially different screening and treatment modalities, we sought to examine the relationship between urothelial carcinoma of the renal pelvis (rUC) and urothelial carcinoma of the bladder (bUC). Fresh tumor tissue was collected from patients with bUC (n=10) and benign mucosa from the bladder (n=7) was collected from individuals undergoing resection for non-UC conditions for comparison. Gene expression profiles from these samples were determined using high-throughput Affymetrix gene expression microarray chips. Bioinformatic approaches were used to compare gene expression profiles of these samples and those of rUC (n= 14) and normal kidney (n=14) that were mostly used in our previous publication. Using unsupervised analytic approaches, rUC and bUC were indistinguishable. When supervised analytic approach was used, a very small number of potentially differentially expressed genes was identified; these differences were most likely to be limited to a single pathway - the chloride ion binding activity pathway -which was more frequently activated in rUC than in bUC. We found that the gene expression profiles of UCs from the upper and lower tract were extremely similar, suggesting that similar pathogenic mechanisms likely function in the development of these tumors. The differential expression of genes in the identified pathway may represent a potential new avenue for detection of upper tract tumors. Tissue samples with urothelial cell carcinoma from lower tract (bladder) as well as normal references were collected and the gene expression profiles were compared with gene expression profiles of samples in our previously published data set . No technical replicates.
2010-12-31 | E-GEOD-24152 | biostudies-arrayexpress
Project description:This study presents a comprehensive multi-omic analysis of upper urinary tract urothelial tumours (UTUC) and urines of patients with past exposure to carcinogenic aristolochic acid (AA). We determined complex miRNA:mRNA tumor networks and their key protein components. Tumor exome and transcriptome sequencing revealed a burden of AA-specific mutations in UTUC and identified deleteriously mutated genes and their mRNA transcripts. A subset of identified urinary miRNAs presents potential biomarkers of UTUC development or presence. Recurrent upper urinary tract carcinomas (UTUC) arise in the context of nephropathy linked to exposure to the herbal carcinogen aristolochic acid (AA). We aimed to delineate the detailed biological programs underlying UTUC tumorigenesis in patients from endemic aristolochic acid nephropathy (AAN) regions in Southern Europe, by using an integrative multi-omics analysis of UTUCs, corresponding unaffected tissues and of patient urines. Quantitative miRNA and mRNA expression profiling, immunohistochemical analysis by tissue microarrays, and exome and transcriptome sequencing were performed in UTUC and non-tumor tissues. Urinary miRNAsof cases undergoing surgery were profiled before and after UTUC resection. RNA and protein levels were analyzed using appropriate statistical tests and trend assessment. Dedicated bioinformatic tools were used for analysis of pathways, mutational signatures and result visualization. The results delineate UTUC-specific miRNA:mRNA networks comprising 89 miRNAs associated with 1862 target mRNAs and involving deregulation of cell cycle, DNA damage response, DNA repair, bladder cancer, oncogenes, tumor suppressors, chromatin structure regulators and developmental signaling pathways. Key UTUC-specific transcriptome components were confirmed at the protein level. Exome and transcriptome sequencing of UTUC revealed AA-specific COSMIC mutational signature 22, with 68-76% AA-specific, deleterious mutations propagated at the mRNA level. We next identified a signature of UTUC-specific miRNAs consistently more abundant in the patients’ urine prior to tumor resection. The gene regulation programs of AAN-associated UTUC tumors are highly complex and involve regulatory miRNAs prospectively applicable to non-invasive urine-based screening of AAN patients for cancer recurrence.
2021-06-30 | GSE166716 | GEO
Project description:This study presents a comprehensive multi-omic analysis of upper urinary tract urothelial tumours (UTUC) and urines of patients with past exposure to carcinogenic aristolochic acid (AA). We determined complex miRNA:mRNA tumor networks and their key protein components. Tumor exome and transcriptome sequencing revealed a burden of AA-specific mutations in UTUC and identified deleteriously mutated genes and their mRNA transcripts. A subset of identified urinary miRNAs presents potential biomarkers of UTUC development or presence. Recurrent upper urinary tract carcinomas (UTUC) arise in the context of nephropathy linked to exposure to the herbal carcinogen aristolochic acid (AA). We aimed to delineate the detailed biological programs underlying UTUC tumorigenesis in patients from endemic aristolochic acid nephropathy (AAN) regions in Southern Europe, by using an integrative multi-omics analysis of UTUCs, corresponding unaffected tissues and of patient urines. Quantitative miRNA and mRNA expression profiling, immunohistochemical analysis by tissue microarrays, and exome and transcriptome sequencing were performed in UTUC and non-tumor tissues. Urinary miRNAsof cases undergoing surgery were profiled before and after UTUC resection. RNA and protein levels were analyzed using appropriate statistical tests and trend assessment. Dedicated bioinformatic tools were used for analysis of pathways, mutational signatures and result visualization. The results delineate UTUC-specific miRNA:mRNA networks comprising 89 miRNAs associated with 1862 target mRNAs and involving deregulation of cell cycle, DNA damage response, DNA repair, bladder cancer, oncogenes, tumor suppressors, chromatin structure regulators and developmental signaling pathways. Key UTUC-specific transcriptome components were confirmed at the protein level. Exome and transcriptome sequencing of UTUC revealed AA-specific COSMIC mutational signature 22, with 68-76% AA-specific, deleterious mutations propagated at the mRNA level. We next identified a signature of UTUC-specific miRNAs consistently more abundant in the patients’ urine prior to tumor resection. The gene regulation programs of AAN-associated UTUC tumors are highly complex and involve regulatory miRNAs prospectively applicable to non-invasive urine-based screening of AAN patients for cancer recurrence.
2021-06-30 | GSE166909 | GEO
Project description:This study presents a comprehensive multi-omic analysis of upper urinary tract urothelial tumours (UTUC) and urines of patients with past exposure to carcinogenic aristolochic acid (AA). We determined complex miRNA:mRNA tumor networks and their key protein components. Tumor exome and transcriptome sequencing revealed a burden of AA-specific mutations in UTUC and identified deleteriously mutated genes and their mRNA transcripts. A subset of identified urinary miRNAs presents potential biomarkers of UTUC development or presence. Recurrent upper urinary tract carcinomas (UTUC) arise in the context of nephropathy linked to exposure to the herbal carcinogen aristolochic acid (AA). We aimed to delineate the detailed biological programs underlying UTUC tumorigenesis in patients from endemic aristolochic acid nephropathy (AAN) regions in Southern Europe, by using an integrative multi-omics analysis of UTUCs, corresponding unaffected tissues and of patient urines. Quantitative miRNA and mRNA expression profiling, immunohistochemical analysis by tissue microarrays, and exome and transcriptome sequencing were performed in UTUC and non-tumor tissues. Urinary miRNAsof cases undergoing surgery were profiled before and after UTUC resection. RNA and protein levels were analyzed using appropriate statistical tests and trend assessment. Dedicated bioinformatic tools were used for analysis of pathways, mutational signatures and result visualization. The results delineate UTUC-specific miRNA:mRNA networks comprising 89 miRNAs associated with 1862 target mRNAs and involving deregulation of cell cycle, DNA damage response, DNA repair, bladder cancer, oncogenes, tumor suppressors, chromatin structure regulators and developmental signaling pathways. Key UTUC-specific transcriptome components were confirmed at the protein level. Exome and transcriptome sequencing of UTUC revealed AA-specific COSMIC mutational signature 22, with 68-76% AA-specific, deleterious mutations propagated at the mRNA level. We next identified a signature of UTUC-specific miRNAs consistently more abundant in the patients’ urine prior to tumor resection. The gene regulation programs of AAN-associated UTUC tumors are highly complex and involve regulatory miRNAs prospectively applicable to non-invasive urine-based screening of AAN patients for cancer recurrence.
2021-06-30 | GSE166907 | GEO
Project description:Treatment paradigms for patients with upper tract urothelial carcinoma (UTUC) are typically extrapolated from studies of bladder cancer despite their distinct clinical and molecular characteristics. A major hurdle to the advancement of UTUC research is the lack of disease-specific models. Here, we report the establishment of patient derived xenograft (PDX) and cell lines models that reflect the heterogeneity of the human disease. Models demonstrated high genomic concordance with the tumors from which they were derived with muscle-invasive tumors more likely to successfully engraft. Treatment of PDX with chemotherapy recapitulated responses observed in the patients. Analysis of a S310F HER2 mutant PDX suggested that an antibody drug conjugate targeting HER2 would have superior efficacy to HER2-selective kinase inhibitors. In sum, the biologic and phenotypic concordance between patient and PDXs suggests that these models could facilitate studies of intrinsic and acquired resistance and the development of personalized medicine strategies for UTUC patients.
2020-01-29 | GSE134292 | GEO