Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE128701 | GEO | 2019/03/23
REPOSITORIES: GEO
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Project description:Impact of Immune and Stromal Infiltration on Outcomes Following Bladder-Sparing Trimodality Therapy for Muscle-Invasive Bladder Cancer
| PRJNA528580 | ENA
Project description:Purpose: While molecular targeted therapy has revolutionized the treatment of many cancers, little progress has been made in the development of novel therapies for muscle invasive bladder cancer (MIBC). Here we report on the establishment and characterization of patient-derived primary MIBC xenografts Tumor fragments derived from 7 patients with MIBC were grafted under the renal capsule of NOD-SCID mice and subsequently transplanted to further mice over multiple generations. Patient tumor and xenograft tissue were processed for analysis of , gene expression by microarray, and expression of select potential target pathways by immunohistochemistry (IHC).
2015-03-27 | E-GEOD-67312 | biostudies-arrayexpress
Project description:Purpose: While molecular targeted therapy has revolutionized the treatment of many cancers, little progress has been made in the development of novel therapies for muscle invasive bladder cancer (MIBC). Here we report on the establishment and characterization of patient-derived primary MIBC xenografts
2015-03-27 | GSE67312 | GEO
Project description:Recently, we described a nerve-sparing mid-urethra model of partial outlet obstruction (NeMO) that has high consistency and minimal mortalities, unlike the traditional model of obstruction proximal to the bladder neck. To uncover pathogenic pathways in PBO, we performed NeMO and examined the transcriptional responses in the bladder. NeMO increased bladder mass, relative bladder mass, hyperactivity and decreased voiding efficiency. In NeMO vs. sham bladders, there were 831 differentially expressed genes, which correlated significantly with physiologic parameters. Of the 796 genes mapped to human orthologues, upregulated genes were enriched for functions related to extracellular matrix, and cytokine activation, and downregulated genes were enriched for functions relating to muscle contraction and metabolism. To identify candidate drug targets for the treatment of PBO, we analysed the conserved transcriptional response to PBO in human and mouse. Gene sets related to cytokine activation, including the TNF pathway, were consistently upregulated in both human and mouse bladders affected by obstruction, revealing a potential therapeutic target. Accordingly, we depleted macrophages, which are an important source of TNF, with clodronate (CL). In NeMO, CL significantly decreased hyperactive voiding, residual volumes and improved voiding efficiency (p<0.05). Moreover, the expression levels of cytokines/chemokines correlated with several bladder functional parameters. Thus, genes that control progression of pathology in bladder obstruction are consistently dysregulated in NeMO and human bladders affected by PBO, supporting the use of the nerve-sparing mouse obstruction model for therapeutic exploration.
2022-07-27 | GSE209625 | GEO
Project description:Background: The response to neoadjuvant cisplatin-based chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) is impaired in up to 50% of patients due to chemoresistance, with no predictive biomarkers in clinical use. RNA-binding motif protein 3 (RBM3) has emerged as a putative modulator of chemotherapy response but has a hitherto unrecognized role in MIBC. Methods: Tumour-specific RBM3 protein expression was assessed via immunohistochemistry in paired transurethral resection of the bladder (TURB) specimens, cystectomy specimens and lymph node metastases from 145 patients. The effect of RBM3 suppression on chemosensitivity was examined in RT4 and T24 cells in vitro. RNA-sequencing was applied to compare gene expression profiles between siRBM3-treated and control cells. Findings: RBM3 protein expression was significantly higher in TURB compared to cystectomy specimens but showed consistency between primary tumours and lymph node metastases. High tumour-specific RBM3 expression was significantly associated with a reduced risk of recurrence in NAC treated patients. In T24 cells, which displayed higher RBM3 levels than RT4 cells, RBM3 silencing conferred a decreased sensitivity to cisplatin and gemcitabine. RNA-sequencing revealed potential involvement of RBM3 in facilitating cell cycle progression, in particular G1/S-phase transition, and initiation of DNA replication. Interpretation: The presented data highlight the predictive value of RBM3 in MIBC, which could, if prospectively validated, improve treatment stratification of patients with this aggressive disease.
2022-01-11 | GSE167558 | GEO
Project description:Muscle-invasive bladder cancer (MIBC) is an aggressive disease with high morbidity and mortality that can be divided into basal and luminal subtypes based on genomic characteristics. Due to the complex heterogeneity of MIBC, specific markers are needed to distinguish MIBC subtypes to guide future clinical treatment. In this study, we explore abnormal lncrnas that are specific to the basic and intracavitary subtypes of MIBC, which will provide potential biomarkers for precision therapy of MIBC.
2023-04-14 | GSE229410 | GEO
Project description:INTRODUCTION: Progressive muscle-invasive bladder cancer (MIBC) has more aggressive behavior than de novo MIBC. This study aimed to ascertain the differences in gene expression profiles between both MIBC groups and to identify prognostic biomarkers to improve the treatment in these patients. MATERIAL AND METHODS: Retrospective multicentre study in which 212 MIBC patients (104 progressive and 108 de novo) who underwent radical cystectomy in the Hospital Clinic (Barcelona) and Radboud UMC (Nijmegen) were included. Total RNA from formalin-fixed paraffin-embedded tissue samples was obtained. Gene expression profiles of 27,965 coding transcripts were determined in 26 patients using Illumina microarrays. Expression levels of 94 genes selected from microarray data and literature were studied by quantitative PCR in an independent series of 186 de novo and progressive MIBC patients. Survival analysis was performed with the Kaplan-Meier method. R-software and SPSSv23 were used for all calculations. RESULTS: A total of 480 genes were found differently expressed (FDR<0.01) between progressive and de novo MIBC samples. Differential expression of 23 out of the 94 genes selected was validated in an independent set of samples. Survival analysis showed that expression of eight genes were prognostic factors of BCR. CONCLUSION: De novo and progressive MIBC patients show different gene expression profiles. In addition, we have identified eight genes with prognostic value which may contribute to improve BC risk stratification and, consequently, to tailor treatment and surveillance strategies in these patients.
2021-03-23 | GSE149582 | GEO
Project description:Purpose: Selecting muscle-invasive bladder cancer patients for adjuvant therapy is currently based on clinical variables with limited power. We hypothesized that genomic-based signatures can outperform clinical models to identify patients at higher risk. Method:Transcriptome-wide expression profiles were generated using 1.4 million feature-arrays on archival tumors from 225 patients who underwent radical cystectomy and had muscle-invasive and/or node-positive bladder cancer. A 15-feature GC was developed on the discovery set with area under curve (AUC) of 0.77 in the validation set. A cohort comprised of 225 patients with organ-confined, muscle-invasive (pT2N0M0),extravesical (pT3-4aN0M0), and node-positive (pTanyN1-3M0) UCB who underwent radicalcystectomy at the University of Southern California between 1998 and 2004 was used. Each patient had aminimum two-year follow-up post-cystectomy unless they recurred prior to that date. Patients receiving neoadjuvant chemotherapy, and those with clinical evidence of lymphadenopathy or distant metastasis at diagnosis were excluded.
2014-10-27 | E-GEOD-57933 | biostudies-arrayexpress
Project description:miRNAs are involved in cancer development and progression,acting as tumor suppressors or oncogenes. Half of the human miRNAs are located in cancer-associated genomic regions and can function as tumor suppressor genes or oncogenes depending on their targets miRNA profiling was performed on paired bladder cancer tissues and differentially expressed miRNAs were identified in BC and adjacent noncancerous tissues of any disease stage/grade. Ten paired bladder cancer tissues (5 low-grade non-muscle-invasive bladder cancer[NMIBC] and 5 high-grade muscle-invasive bladder cancer[MIBC]) were sent to CapitalBio Corp. (Beijing) for noncoding RNA microarray analysis. The microarray analysis was done as described on the Web site of CapitalBio. NMIBC samples include 07A, 19A, 23A, 24A and T63 while coresponding pairs include 07B, 19B, 23B, 24B and 63. MIBC samples include 10A, 20A, 21A, 34A and 49A while coresponding pairs include 10B, 20B, 21B, 34B and 49B.
2012-07-06 | E-GEOD-39093 | biostudies-arrayexpress
Project description:A Cartes dM-^RIdentite des Tumeurs (CIT) project from the french Ligue Nationale Contre le Cancer (http://cit.ligue-cancer.net/). Seven transcriptome datasets corresponding to a new series of 85 MIBC (Muscle-invasive bladder cancer) and six publicly-available series (298 MIBC) were analyzed. Tumors were classified by consensus clustering. Overall survival was determined from Kaplan-Meier curves. The role of the EGFR pathway was investigated by pathway bioinformatics analysis, determination of the expression levels of its components (by microarray, RT-qPCR and western blot) and of EGFR copy number by CGH arrays. A 40-gene transcriptomic classifier was used to identify basal-like cell lines and a basal-like mouse model. Please note M-^QMIBC molecular subtype': tumors classification using consensus clustering.
2014-06-01 | E-MTAB-1803 | biostudies-arrayexpress