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

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

PROVIDER: PRJNA735225 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14735900_1.fastq.gz	Fastqsanger.gz
	SRR14735900_2.fastq.gz	Fastqsanger.gz
	SRR14735901_1.fastq.gz	Fastqsanger.gz
	SRR14735901_2.fastq.gz	Fastqsanger.gz
	SRR14735902_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:Background: Intravesical bacillus Calmette-Guérin (BCG) therapy is standard treatment for high-risk non-muscle invasive bladder cancer (NMIBC) but overall efficacy is low, and no reliable predictive biomarkers currently exist to refine patient selection. We performed genomic analysis on high-grade (HG) T1 NMIBCs to determine if response to therapy is predicted by certain mutational and/or expressional changes. Methods: Patients with HG T1 NMIBC treated with induction BCG were stratified by response into durable and non-durable responders. Tumor samples were subjected to whole-exome RNA sequencing. Gene expression and variant analysis were performed on RNA sequencing to identify changes between BCG durable responders and those that did not respond. Results: Differentially expressed genes in durable responders were input into IPA and identified associated immune related pathways: MIF-mediated Glucocorticoid Regulation, MIF Regulation of Innate Immunity, and p38 MAPK Signaling. The differentially expressed genes were crossed with RNAseq variant analysis to identify genes that had significant changes in both. This analysis identified JCHAIN, S100A7, CLECB, and ANXA10 genes that had snps in non-durable responders vs durable responders and also had significant change in gene expression between these two groups. Conclusions: Differences in the genomic profiles of HG T1 NMIBC tumors exist between those who show durable response to BCG and those who do not. Using pathway analysis, those differences imply upregulation of several interconnected inflammatory pathways among responders. Specific variants identified here are candidates for further study and, if clinically validated, may serve as useful biomarkers in the future.

2021-06-05 | GSE176178 | GEO

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

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.

2021-12-06 | GSE156422 | GEO

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

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.

| EGAS00001004764 | EGA

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

Early transcriptomic response of innate immune cells to subcutaneous BCG vaccination of mice

Project description:Bacille Calmette-Guerin (BCG) vaccination might contribute to nonspecific enhancement of resistance to various infections. Thus, BCG in addition to the formation of specific immunity against mycobacteria is also capable of inducing “trained immunity” - the ability of the innate immune system to maintain the memory of past infections and use it to develop immune defenses against new ones. In this study, we performed RNA sequencing of innate immune cells derived from mice bone marrow and spleen three day after subcutaneous BCG vaccination to evaluate early transcriptomic response of innate immune cells

2024-05-20 | GSE261448 | GEO

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

Mycobacterium tuberculosis variant bovis BCG strain:Bacillus Calmette-Guerin | isolate:M1_S49

Project description:Mycobacterium tuberculosis variant bovis BCG strain:Bacillus Calmette-Guerin | isolate:M1_S49 Genome sequencing and assembly

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Maternal BCG scar is associated with enhanced infant proinflammatory responses

Project description:Prenatal exposures such as infections and immunisation may influence infant responses. We had an opportunity to undertake an analysis of responses in infants within the context of a study investigating the effects of maternal mycobacterial exposures and infection on bacille Calmette-Guerin (BCG) vaccine-induced responses in Ugandan infants. Gene expression profiles for pathways associated with maternal LTBI and with maternal BCG scar were examined using samples collected at one (n=42) and six (n=51) weeks after BCG immunisation using microarray. Interferon and inflammation response pathways were up-regulated in infants of mothers with LTBI at six weeks, and in infants of mothers with a BCG scar at one and six weeks after BCG immunisation. Maternal BCG scar had a stronger association with infant responses than maternal LTBI, with an increased proinflammatory immune profile.

2016-10-12 | GSE87801 | GEO

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