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ABSTRACT: Genomic Analysis of Response to Bacillus Calmette-Guerin (BCG) Treatment in High-Grade Stage 1 Bladder Cancer Patients

PROVIDER: PRJNA736154 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14763500_1.fastq.gz	Fastqsanger.gz
	SRR14763500_2.fastq.gz	Fastqsanger.gz
	SRR14763501_1.fastq.gz	Fastqsanger.gz
	SRR14763501_2.fastq.gz	Fastqsanger.gz
	SRR14763502_1.fastq.gz	Fastqsanger.gz

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Genomic Analysis of Response to Bacillus Calmette-Guerin (BCG) Treatment in High-Grade Stage 1 Bladder Cancer Patients

Project description:Genomic Analysis of Response to Bacillus Calmette-Guerin (BCG) Treatment in High-Grade Stage 1 Bladder Cancer Patients

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Longitudinal Transcription Profiling of Bladder Cancers Dictate the Response to BCG Treatment and Disease Progression

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.

2023-12-25 | GSE244895 | GEO

Glutathione-S-transferase theta 2 (GSTT2) modulates the tumor microenvironment and the response to BCG immunotherapy in a murine orthotopic model of bladder cancer

Project description:Whilst M. bovis Bacillus Calmette-Guérin (BCG) therapy remains the gold-standard for treatment of high-risk non-muscle invasive bladder cancer (BC), 30-40% of patients fail therapy, resulting in disease recurrence and progression. Loss of glutathione-S-transferase theta 2 (GSTT2) expression has been associated with improved response to fewer instillations of BCG. To understand these responses, wild-type (WT) and GSTT2-knockout (KO) mice were implanted orthotopically with MB49-PSA BC cells, and mice were treated with four weekly BCG instillations, after which the bladders were harvested for single-cell RNA sequencing.

2024-12-11 | GSE281932 | GEO

Immunological hallmarks for clinical response to BCG in bladder cancer

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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Transcriptional signature of BCG vaccination

Project description:The century-old Mycobacterium bovis Bacillus Calmette-Guerin (BCG) remains the only licensed vaccine against tuberculosis (TB). Despite this, there is still a lot to learn about the immune response induced by BCG, both in terms of phenotype and specificity. Here, we investigated the BCG-specific gene expression changes induced in PBMCs and CD4 memory T cells by BCG in individuals pre- and 8m post vaccination. We also determined whether reactivity against a peptide pool defined in individuals with controlled latent TB infection (MTB300), and with peptides homologous to peptides found in BCG, was boosted following BCG vaccination.

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Exploring the potential role of moonlighting function of the surface-associated proteins from Mycobacterium bovis BCG Moreau and Pasteur by comparative proteomic

Project description:Tuberculosis (TB) is one of major causes of death worldwide. Bacillus Calmette-Guerin (BCG) is the only licensed TB vaccine and its inability to protect against adult pulmonary TB can be due to genetic differences among strains described since the 1940s. In this work, we compared the proteomic profile of the surface-associated proteins from M. bovis BCG Moreau, the Brazilian vaccine strain, and the BCG Pasteur reference strain. The methodology used was 2D-gel electrophoresis combined with mass spectrometry techniques (MALDI-TOF/TOF). We identified 115 proteins. Of these, 24 proteins showed differential expression between the two BCG strains. Furthermore, 27 proteins previously described as displaying moonlighting function were identified, 8 of these proteins showed variation in abundance comparing BCG Moreau to Pasteur and 2 of them presented two different domain hits.

2019-05-15 | PXD006141 | Pride

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Project description:This ordinary differential equation model, simulating the tumor-immune interactions involved in BCG immunotherapy to treat superficial bladder cancer, is described by the publication: Bunimovich-Mendrazitsky, S., Shochat, E., Stone, L. "Mathematical Model of BCG Immunotherapy in Superficial Bladder Cancer". Bull. Math. Biol. 69, 1847–1870 (2007). DOI: 10.1007/s11538-007-9195-z Comment: This model is based on the system of ODEs given in Equation 4 of the publication manuscript. Reproduction of Figure 4 was achieved by setting p4 = 0.085. Abstract: Immunotherapy with Bacillus Calmette-Guérin (BCG)-an attenuated strain of Mycobacterium bovis (M. bovis) used for anti tuberculosis immunization-is a clinically established procedure for the treatment of superficial bladder cancer. However, the mode of action has not yet been fully elucidated, despite much extensive biological experience. The purpose of this paper is to develop a first mathematical model that describes tumor-immune interactions in the bladder as a result of BCG therapy. A mathematical analysis of the ODE model identifies multiple equilibrium points, their stability properties, and bifurcation points. Intriguing regimes of bistability are identified in which treatment has potential to result in a tumor-free equilibrium or a full-blown tumor depending only on initial conditions. Attention is given to estimating parameters and validating the model using published data taken from in vitro, mouse and human studies. The model makes clear that intensity of immunotherapy must be kept in limited bounds. While small treatment levels may fail to clear the tumor, a treatment that is too large can lead to an over-stimulated immune system having dangerous side effects for the patient.

2024-09-02 | BIOMD0000001034 | BioModels

Quantitative proteomic analysis of tumor tissues before and during Bacillus Calmette-Guérin instillation in bladder cancer

Project description:The alteration of protein expression profile mediated by Bacillus Calmette-Guérin (BCG) treatment remains unclear and is rarely studied. Three paired before BCG(pre-BCG) and during BCG(on-BCG) tissues were collected for proteomicsanalyses to describe the proteomic changes caused by BCG.

2024-11-04 | PXD055011 | Pride

Identification of a Novel Inflamed Tumor Microenvironment Signature as a Predictive Biomarker of Bacillus Calmette-Guérin Immunotherapy in Non–Muscle-Invasive Bladder Cancer

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.

2021-10-05 | GSE185264 | GEO

Project description:MICROECOLOGICAL MECHANISMS OF INTRAVESICAL BACILLUS CALMETTE GUERIN TREATMENT IN PATIENTS WITH UROTHELIAL BLADDER CANCER

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