Whole transcriptome sequencing for upper tract urothelial carcinoma (UTUC) of BALB/c female mice treated with N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE274057 | GEO | 2024/11/16
REPOSITORIES: GEO
Dataset's files
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| GSE274057_F4594_d336_raw_count_for_iDEP.tsv.gz | Tabular |
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Project description:To know the biological characteristics of UTUC, we conducted the RNA-seq.
2024-11-16 | GSE275638 | 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: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: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
Project description:Purpose: upper tract urothelial carcinoma (UTUC) is the predominant subtype of the renal pelvis carcinoma but current knowledge about the molecular properties and prognostic markers is sparse. In this study, we examined the genome-wide mRNA expression spectrum of UTUC aiming to characterize the molecular basis of this cancer, and identify potential prognostic markers and thus facilitate the clinical practices. Experimental Design: we compared the whole mRNA expression spectrum of cancer and matched normal tissues in 10 patients with UTUC using massively parallel sequencing, thereafter the protein levels and prognostic roles of ALDH2, CCNE1 and SMAD3 were evaluated under an independent validation set comprising of 104 patients. Results: mRNA down-regulation of ALDH2 and up-regulation of SMAD3 and CCNE1 in UTUC were revealed by expression profiling. And low protein expression of ALDH2 was associated with an adverse outcome for patients (p < 0.0001). Whereas high CCNE1 and SMAD3 were associated with adverse clinical outcome (p < 0.0001). And multivariate analysis revealed that all these three molecular markers were independent prognostic predictors. Besides, compared to the pathological TNM classification, All ALDH2, CCNE1 and SMAD3 were more competent in identifying patient subgroup with high mortality risk, and the molecular markers were able to predict the survival difference in the patients of T2 and T3 subgroup (p < 0.001), which could not be achieved by TNM staging. Conclusions: This is the first prospective study that characterizes genome-wide mRNA expression profile of UTUC. We revealed the prognostic significance of ALDH2, CCNE1 and SMAD3, and these molecular marker were more robust than TNM system in clinical outcome prediction.
2015-01-01 | GSE47702 | GEO
Project description:Upper tract urothelial carcinoma (UTUC) is often diagnosed late and exhibits poor prognosis. Only limited data are available concerning potential noninvasive biomarkers for disease monitoring. Here, we investigated the proteomic profile of plasma in 362 UTUC patients and 239 healthy control samples. The results show 520 elevated proteins in UTUC patients are mainly involved in acute-phase response and tRNA aminoacylation pathways; while 317 descend proteins are enriched in sulfur metabolism and deubiquitination. We presented an integrated tissue-plasma proteomic approach to infer the highly specific tumor biomarkers for identify patients with muscle-invasive UTUC. We provided a protein panel that reflected lymph node metastasis, which is of interest to identify high risk and poor prognosis UTUC patients. We also identified a ten-gene signature and establishment of a prognostic nomogram predicting progression-free survival of UTUC. Finally, we further validated the biomarkers by parallel reaction monitoring (PRM) assay in a new independent cohort.
2023-07-12 | PXD043774 |
Project description:Analyses of large transcriptomics datasets of muscle-invasive bladder cancer (MIBC) has led to a consensus classification. Molecular subtypes of upper tract urothelial carcinomas (UTUC) are less known. Our objective was to determine the relevance of consensus classification in UTUCs by characterizing a novel cohort of surgically treated ≥pT1 tumors.Subtype IHC markers GATA3-CK5/6-TUBB2B in multiplex, CK20, p16 and Ki67, MMR proteins, PD-L1 IHC were evaluated. Heterogeneity was assessed morphologically and/or with subtype IHC. FGFR3 mutations were identified by pyrosequencing. We performed 3’RNA-seq, including with multisampling in heterogeneous cases. Consensus classes, unsupervised groups, and microenvironment cell abundance were determined using gene expression.Most of the 66 patients were men (77.3%), with pT1 (n=23, 34.8%) or pT2-4 stage UTUC (n=43, 65.2%). FGFR3 mutations and dMMR status were identified in 40% and 4.7% of cases, respectively. Consensus subtypes robustly classified UTUCs and reflected intrinsic subgroups. All pT1 tumors were classified as Luminal papillary (LumP). Combining our consensus classification results to that of previously published UTUC cohorts, LumP tumors represented 57.2% of ≥pT2 UTUC, which was significantly higher than in MIBC. Ten patients (15.2%) harbored areas of distinct subtypes. Consensus classes were associated with FGFR3 mutations, stage, morphology and IHC. The majority of LumP tumors were characterized by low immune infiltration and PD-L1 expression, in particular if FGFR3 mutated.
2023-10-10 | GSE244957 | GEO
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:Prognostic biomarkers including microRNAs(miRNAs) and genes in upper tract urothelial carcinomas (UTUCs) originating from the renal pelvis and ureter account for only 5% to 10% of all UCs, but this figure is markedly higher in Taiwan, where it can reach up to 30%. By using next-generation sequencing (NGS), we analysed two pairs of renal pelvis tumours and adjacent normal urothelial tissues to screen miRNAs and messenger RNAs. By combining bioinformatics analysis from miRmap, Gene Expression Omnibus (GEO), and Oncomine and Ingenuity® Pathway Analysis databases, we identified candidate genes. To search upstream miRNAs with exact target binding sites, we used miRmap, TargetScan, and miRDB to enforce evidence. Then, we clarified gene and protein expression through an in vitro study. After interaction of the selected target genes obtained using the NGS and miRmap methods were analysed through a Venn diagram analysis, six potential genes—namely, PDE5A, RECK, ZEB2, NCALD, PLCXD3, CYBRD1—presenting significant differences were distinguished. Further analysis of gene expression indicated lower expression of that PDE5A, RECK, ZEB2, and CYBRD1 in bladder cancer tissue than in normal bladder mucosa, which indicated that PDE5A, RECK, ZEB2, and CYBRD1 may act as tumour suppressors in UTUC. In addition, we identified putative oncomiRs in miR-181c-5p target sites on PDE5A, miR-200c-3p target sites on RECK, and miR-200bc-3p/429 target sites on ZEB2. Compared with normal tissue, lower PDE5A expression in tumour specimens was demonstrated in paired UTUC tissues (normal and tumour) from 20 patients. Our findings suggest that both candidate miRNAs and regulated genes may play crucial roles in UTUC progression. We propose that these markers may be potential targets in both diagnostic and therapeutic strategies as clarified by in vitro and in vivo experiments. PDE5A also potentially presents tumour suppressor genes, as identified by comparing the expression between normal and tumour specimens from 10 patients.
2021-04-06 | GSE159824 | GEO