Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1144434 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30131700_1.fastq.gz | Fastqsanger.gz | |||
| SRR30131700_2.fastq.gz | Fastqsanger.gz | |||
| SRR30131701_1.fastq.gz | Fastqsanger.gz | |||
| SRR30131701_2.fastq.gz | Fastqsanger.gz | |||
| SRR30131702_1.fastq.gz | Fastqsanger.gz |
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Project description:Improved risk stratification and predictive biomarkers of treatment response are needed for non–muscle-invasive bladder cancer (NMIBC). Here we assessed the clinical utility of targeted RNA and DNA molecular profiling in NMIBC. We performed RNA-based profiling by NanoString nCounter on non–muscle-invasive bladder cancer (NMIBC) clinical specimens and found that a novel expression signature of an inflamed tumor microenvironment (TME), but not molecular subtyping, was associated with improved recurrence-free survival after bacillus Calmette-Guérin (BCG) immunotherapy. We further demonstrated that immune checkpoint gene expression was not associated with higher recurrence rates after BCG.
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Project description:Intravesical Bacillus Calmette-Guerin (BCG) is an effective immunotherapy for non-muscle invasive bladder cancer (NMIBC). However, recurrence and progression remain frequent warranting deeper insights into its mechanism. We herein comprehensively profiled blood and tissues obtained from NMIBC patients before, during and after BCG treatment using cytometry by time-of-flight (CyTOF) and RNA sequencing to identify the key immune subsets crucial for anti-tumour activity.
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Project description:Although the intravesical instillation of Bacillus Calmette-Guerin (BCG) is widely used as adjuvant treatment for nonmuscle-invasive bladder cancers, the clinical benefit is variable across patients, and the molecular mechanisms underlying the sensitivity to BCG administration and disease progression are poorly understood. To establish the molecular signatures that predict the responsiveness and disease progression of bladder cancers treated with BCG, we performed transcriptome sequencing (RNA-seq) for 13 treatment-naïve and 22 post-treatment specimens obtained from 14 bladder cancer patients. To overcome disease heterogeneity, we used non-negative matrix factorization to identify the latent molecular features associated with drug responsiveness and disease progression. At least 12 molecular features were present, among which the immune-related feature was associated with drug responsiveness, indicating that pre-treatment anti-cancer immunity might dictate BCG responsiveness. We also identified disease progression-associated molecular features indicative of elevated cellular proliferation in post-treatment specimens. The progression-associated molecular features were validated in an extended cohort of BCG-treated bladder cancers. Our study advances understanding of the molecular mechanisms of BCG activity in bladder cancers and provides clinically relevant gene markers for evaluating and monitoring patients.
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Project description:Dataset for the paper: Non-muscle Invasive Bladder Cancer Molecular Subtypes Predict Differential Response to Intravesical Bacillus Calmette-Guérin
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Project description:Trained immunity is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to certain microbial components, altering their responses to future exposures. Intravesical instillation with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant therapy in patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC). HR-NMIBC is associated with a high risk of tumor recurrence and progression to muscle-invasive bladder cancer. The precise immunological mechanisms through which BCG mediates anti-tumor immunity are still unclear. The aim of our study was to investigate the (long-term) induction of trained immunity by repeated BCG instillations in NMIBC patients and elucidate the immunological and epigenetic mechanisms that are involved. Another aim was to assess the relationship between trained immunity response and clinical response of NMIBC patients, in terms of recurrence free survival and progression free survival. To determine whether BCG instillations induce trained immunity in peripheral blood mononuclear cells (PBMCs) we performed a prospective cohort study (‘Tribute’) and isolated PBMCs collected before BCG therapy and at 8 time points during BCG therapy. A total of 17 BCG-naïve HR-NMIBC patients were included. After isolation of PBMCs, monocytes were further purified using an isolation procotol with a percoll gradient. RNA was isolated from these purified monocytes were and used as input for RNA-seq analysis.
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Project description:Trained immunity is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to certain microbial components, altering their responses to future exposures. Intravesical instillation with Bacillus Calmette-Guérin (BCG) is the most effective adjuvant therapy in patients with high-risk non-muscle invasive bladder cancer (HR-NMIBC). HR-NMIBC is associated with a high risk of tumor recurrence and progression to muscle-invasive bladder cancer. The precise immunological mechanisms through which BCG mediates anti-tumor immunity are still unclear. The aim of our study was to investigate the (long-term) induction of trained immunity by repeated BCG instillations in NMIBC patients and elucidate the immunological and epigenetic mechanisms that are involved. Another aim was to assess the relationship between trained immunity response and clinical response of NMIBC patients, in terms of recurrence free survival and progression free survival. To determine whether BCG instillations induce trained immunity in peripheral blood mononuclear cells (PBMCs) we performed a prospective cohort study (‘Tribute’) and isolated PBMCs collected before BCG therapy and at 8 time points during BCG therapy. A total of 17 BCG-naïve HR-NMIBC patients were included. After isolation of PBMCs, monocytes were further purified using an isolation procotol with a percoll gradient. RNA was isolated from these purified monocytes were and used as input for RNA-seq analysis.
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Project description:All mRNA sequencing data were acquired from single patients (BC159T) at a different time (BC159-T#1, BC159-T#2, and BC159-T#3). The first transurethral resection of bladder tumor (TUR-BT) (BC159-T#1) was diagnosed with non-MIUBC (muscle-invasive urothelial bladder cancer). Despite of intravesical bacillus Calmette-Guerin (BCG), the patient progressed into MIUBC at the second TUR-BT (BC159-T#2). After undergoing multiple neoadjuvant chemotherapy regimens (gemcitabine/paclitaxel and sequential paclitaxel), the patient developed local recurrence and multiple lung metastases and removed following palliative partial cystectomy (BC159-T#3).
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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
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