Single-Cell Profiling of Murine Bladder Cancer Identifies Sex Specific Transcriptional Signatures with Prognostic Relevance
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ABSTRACT:
PROVIDER: PRJNA953336 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24108370_1.fastq.gz | Fastqsanger.gz | |||
| SRR24108370_2.fastq.gz | Fastqsanger.gz | |||
| SRR24108371_1.fastq.gz | Fastqsanger.gz | |||
| SRR24108371_2.fastq.gz | Fastqsanger.gz | |||
| SRR24108372_1.fastq.gz | Fastqsanger.gz |
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Project description:Bladder cancer (BLCA) is more common in men but more aggressive in women. A common model used to study sex-based differences in cancer biology is murine BLCA generated by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). While tumors in this model have been profiled, these profiles provided limited information on the tumor microenvironment. Hence, we applied single-cell RNA sequencing to characterize cell type specific transcriptional differences between male and female BBN induced tumors and then studied their human relevance. We found proportion and gene expression differences in the epithelial and non-epithelial subpopulations between male and female tumors. Of translational importance, expression of several genes was found to predict sex specific survival in several human BLCA datasets. We also noted a male biased CD8 T cell exhaustion program in this model that correlates highly with androgen receptor activity. Our study identified novel and clinically relevant sex specific transcriptional signatures and validates the relevance of the BBN model for studying sex differences in human BLCA. This work highlights the importance of considering sex as a biological variable in cancer marker development.
2023-08-09 | GSE229168 | GEO
Project description:Bladder cancer (BLCA) is more common in men but more aggressive in women. Sex-based differences in cancer biology are commonly studied using a murine model with BLCA generated by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). While tumors in the BBN model have been profiled, these profiles provide limited information on the tumor microenvironment. Here, we applied single-cell RNA sequencing to characterize cell-type specific transcriptional differences between male and female BBN-induced tumors. We found proportional and gene expression differences in epithelial and non-epithelial subpopulations between male and female tumors. Expression of several genes predicted sex-specific survival in several human BLCA datasets. We identified novel and clinically relevant sex-specific transcriptional signatures including immune cells in the tumor microenvironment and it validated the relevance of the BBN model for studying sex differences in human BLCA. This work highlights the importance of considering sex as a biological variable in the development of new and accurate cancer markers.
| S-EPMC10494466 | biostudies-literature
Project description:Background Bladder cancer (BC) remains a prevalent malignancy worldwide, with rising incidence rates each year. Despite progress in therapeutic strategies, many patients suffer recurrence or progression, emphasizing the urgent need for novel prognostic biomarkers and therapeutic targets. This research evaluated the prognostic relevance and functional role of Cleavage and Polyadenylation Specificity Factor 3 (CPSF3) in BC. Methods We analyzed CPSF3 expression using The Cancer Genome Atlas data and immunohistochemistry on a cohort of 203 BC patients. A nomogram incorporating CPSF3 expression was developed based on CPSF3 expression for prediction of overall survival and disease-free survival. Immune infiltration analyses and transcriptome sequencing were performed to explore underlying biological mechanisms. In vitro and in vivo experiments were utilized to examine the results of CPSF3 silencing on bladder cancer cell growth, colony-forming ability and cell cycle transitions. Results Elevated CPSF3 expression was significantly linked to unfavorable overall survival and disease-free survival both in TCGA datasets and our cohort. The CPSF3-based nomogram outperformed conventional prognostic models. CPSF3 expression was associated with tumor-infiltrating immune cells and immune checkpoint markers. Enrichment analysis revealed CPSF3 enrichment in cell cycle-related pathways. Suppression of CPSF3 expression led to marked reductions in cell proliferation, colony formation, tumor growth in animal models and inhibited G1 to S phase progression. Conclusion CPSF3 is a promising prognostic biomarker for BC and may play a crucial role in BC progression. Incorporating CPSF3 into clinical prognostic models may enhance prediction of patient outcomes. CPSF3 may represent a promising therapeutic target for BC management.
2025-09-14 | GSE307514 | GEO
Project description:To evaluate the prognostic relevance of molecular subtypes and key transcription factors in pancreatic ductal adenocarcinoma (PDAC), we performed gene expression analysis of whole-tumor tissue obtained from 118 surgically resected PDAC and 13 control samples.
2016-08-17 | GSE62165 | GEO
Project description:Previous studies successfully revealed molecular characteristics of bladder cancers, dealing with non-muscle invasive bladder cancer and muscle invasive bladder cancer, separately. At the molecular level, however, there is a great need to aggregate these subtypes, which may share biological characteristics. This study aimed to identify distinct molecular subtypes of BC and the clinical and/or biological characteristics of each subtype. We used seven gene expression data sets for bladder cancer, which included data from 118 primary bladder cancer samples and 27 recurrent bladder tumor tissues from the Yonsei University Severance Hospital. Hierarchical clustering revealed four molecular subtypes of BC with different clinical outcomes: class 1 with low-grade NMIBC and the best prognosis; class 2 characterized by active FGFR3 and inhibited immune response pathways; class 3 with high-grade NMIBC and the worst progression-free survival; and class 4 mainly comprised of MIBC along with EMT activation. By applying the classifier based on these characteristics, we stratified all BC samples into newly identified molecular subtypes. When comparing previously reported subtypes, our subtypes well agreed with their molecular characteristics regardless of breast cancer-based biology, and showed a strong prognostic relevance in class 3. Integrative analysis of mutation and gene expression suggested that class 3 may have the potential benefit from anti-PD-L1 immunotherapy. Our classifier, constructed by NMIBC and MIBC integration, successfully stratified BC patients into distinct subtypes with different clinical outcomes and a possible treatment option.
2018-10-03 | GSE120736 | GEO
Project description:Genomic Landscape of Young-Onset Bladder Cancer and Its Prognostic Implication on Adult Bladder Cancer
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Project description:Comprehensive investigation identifies CPSF3 as a novel prognostic and oncogenic biomarker in bladder cancer
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Project description:Bladder cancer is common in elderly men, and it is a highly mutated tumor with frequent TP53 and FGFR3 mutation. Young-onset bladder cancer (YBC) is extremely rare; therefore, its genomic characteristics are unknown and appropriate management strategy is yet to be defined. Through a nation-wide search for bladder cancer diagnosed at 20 years or younger, 29 cases of biopsy-proven YBCs were collected. Whole exome sequencing and RNA sequencing were performed on 21 and 11 cases, respectively, and the results were compared with those of adult bladder cancer (ABC) retrieved from public database. Almost all YBCs were low grade, non-invasive papillary tumors. YBC had low mutation burden and less complex copy number alterations. Driver mutations were found in all cases. Common mutations included HRAS mutations (10 cases) with a preference in exon 5 and FGFR3 gene fusions (7 cases) with various partner genes, which occurred in a mutually exclusive manner. Other alterations included KRAS mutations (2 cases), arm-level deletion of chromosomes 4p and 10q (1 case), and ERCC2 mutation (1 case). TP53 and FGFR3 point mutations were not found. The gene expression profiles of YBC corresponded to those of the good prognostic group of ABC. No YBC cases had progressed to muscle-invasive tumor during follow-up. In addition, ABCs with YBC-like mutations also showed no progression to muscle-invasive tumor. In conclusion, YBC had distinct driver genetic alterations such as HRAS mutation and FGFR3 gene fusion and showed good prognosis. YBCs and ABCs with YBC-like mutations may be managed with less aggressive surveillance.
2020-03-30 | GSE133192 | GEO
Project description:Full title: Predictive Gene Signatures as Strong Prognostic Indicators of the Effectiveness of Bacillus Calmetteâ??Guérin (BCG) Immunotherapy in Primary pT1 Bladder Cancers Intravesical BCG immunotherapy is effective in prevention of recurrence and progression in many cases of non-muscle invasive bladder cancer, but many patients fail to respond. This study identified predictive gene signatures in primary pT1 bladder cancer with BCG immunotherapy. Fourty-Eight patients with primary pT1 bladder cancer treated with BCG immunotherapy were used. Microarray gene expression analysis of the 48 primary bladder cancers was carried out. Predictive gene signatures were individually selected based on the recurrence and progression status. Among 43,148 unique genes, 424 and 287 candidate predictive genes that could predict recurrence and progression, respectively, were selected. Time to recurrence or progression was shorter for patients with poor-predictive gene signatures than good-predictive gene signatures (log-rank test, p <0.001, respectively). Validation of predictive gene signatures with RT-PCR was nearly identical to those of microarray (log-rank test, p <0.05, respectively). In multivariate regression analysis, predictive gene signatures were the only independent predictors of recurrence (HR 3.38, p = 0.048) or progression (HR 10.49, p = 0.048) in validation cohorts. Predictive gene signatures have strong diagnostic value for determining the response to intravesical BCG immunotherapy in primary pT1 bladder cancer. Keywords: Gene expression, Bladder cancer, BCG Total RNA, extracted from the fresh frozen tissues of 48 pT1 bladder cancers, was isolated by TRIzol reagent (Life Technologies, NY, USA), according to the manufacturer's protocol. The quality and integrity of the RNA were confirmed by agarose gel electrophoresis and ethidium bromide staining, followed by visual examination under ultraviolet light. Five-hundred nanograms of total RNA were used for labeling hybridization according to the manufacturerâ??s protocol (Illumina HumanWG-6 BeadChip, version 2, Illumina, Inc., San Diego, CA, USA). Arrays were scanned with an Illumina Bead Array Reader confocal scanner (BeadStation 500GXDW; Illumina, Inc.) according to the manufacturer's instructions. Initial microarray gene expression data were obtained using Bead Studio software with gene expression analysis module (version 3.1.3, Illumina, Inc.).
2010-04-07 | E-GEOD-19423 | biostudies-arrayexpress
Project description:Full title: Predictive Gene Signatures as Strong Prognostic Indicators of the Effectiveness of Bacillus Calmette–Guérin (BCG) Immunotherapy in Primary pT1 Bladder Cancers Intravesical BCG immunotherapy is effective in prevention of recurrence and progression in many cases of non-muscle invasive bladder cancer, but many patients fail to respond. This study identified predictive gene signatures in primary pT1 bladder cancer with BCG immunotherapy. Fourty-Eight patients with primary pT1 bladder cancer treated with BCG immunotherapy were used. Microarray gene expression analysis of the 48 primary bladder cancers was carried out. Predictive gene signatures were individually selected based on the recurrence and progression status. Among 43,148 unique genes, 424 and 287 candidate predictive genes that could predict recurrence and progression, respectively, were selected. Time to recurrence or progression was shorter for patients with poor-predictive gene signatures than good-predictive gene signatures (log-rank test, p <0.001, respectively). Validation of predictive gene signatures with RT-PCR was nearly identical to those of microarray (log-rank test, p <0.05, respectively). In multivariate regression analysis, predictive gene signatures were the only independent predictors of recurrence (HR 3.38, p = 0.048) or progression (HR 10.49, p = 0.048) in validation cohorts. Predictive gene signatures have strong diagnostic value for determining the response to intravesical BCG immunotherapy in primary pT1 bladder cancer. Keywords: Gene expression, Bladder cancer, BCG
2010-03-26 | GSE19423 | GEO