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Delineation of tumor, stromal and immune transcriptomes at the infiltrating interface of muscle invasive bladder cancer

肌肉浸润性膀胱癌浸润界面的肿瘤、基质和免疫转录组的描绘

基本信息

批准号：
10543535
负责人：
MARK L DAY
金额：
$ 21.44万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-12-22 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10543535
关键词：
Automobile Driving Bioinformatics Biological Process Bladder Cancer Etiology Cancer Patient Candidate Disease Gene Cells Cellular Indexing of Transcriptomes and Epitopes by Sequencing Cessation of life Clinical Collection Complex Data Set Development Diagnosis Disease Distant Future Gene Expression Gene Expression Profile Genes Genetic Transcription Genomics Heterogeneity Human Immune Individual Infiltration Invaded Malignant neoplasm of urinary bladder Microdissection Molecular Molecular Profiling Muscle Mutation Operative Surgical Procedures Patients Population Process Public Health Publishing Regulator Genes Relapse Research Sampling Submucosa Suspensions Tumor Cell Invasion biomarker development biomarker identification cancer cell cell type gene network immune cell infiltrate improved insight muscle invasive bladder cancer neoplastic cell new therapeutic target potential biomarker predictive marker programs segregation single-cell RNA sequencing transcriptome transcriptome sequencing transcriptomic profiling transcriptomics tumor

项目摘要

Project Summary The presence of tumor invasion into the submucosal muscle of the bladder defines the progression from nonlethal to lethal bladder cancer; however, this process is not well understood at the molecular level. Genomic and transcriptomic profiling of muscle invasive bladder cancer (MIBC) has recently identified mutations and gene expression profiles associated with established MIBC. Although a major advancement in the bladder cancer field, these analyses were unable to determine the unique transcriptional programs activated in individual tumor, stromal and immune populations at the invasive interface of MIBC. This was primarily due to the limitations of accurate spatial collection of infiltrating tumor and adjacent/intermingled stroma and infiltrating immune cells. As a result, earlier transcriptomic studies and even recent studies using single cell RNAseq relied on heterogeneous bulk tumor, which includes both noninvasive as well as normal stroma and immune components spatially distant from the invasive border. This heterogeneity makes it difficult to accurately de-convolute gene expression signatures unique to tumor cells, stroma and infiltrating immune cells in the immediate invasive micro- environment. We hypothesize that distinct gene networks are activated in individual tumor, stromal and immune populations at the invasive interface of MIBC. RNAseq profiling and bioinformatic analysis should reveal enriched and distinct transcriptomic signatures from the individual populations. This research would provide positive impact by identifying cellular and molecular signatures of distinct cellular populations driving invasive progression. These findings could then lead to examination of candidate gene networks that will serve as the basis for biological function, potential biomarker identification and new therapeutic targets that are needed for bladder cancer patients who have been diagnosed with or have relapsed with muscle invasive disease.

项目总结