Delineation of tumor, stromal and immune transcriptomes at the infiltrating interface of muscle invasive bladder cancer
Delineation of tumor, stromal and immune transcriptomes at the infiltrating interface of muscle invasive bladder cancer
批准号:
10353062
负责人:
MARK L DAY
金额:
$18.23万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-12-22 至 2023-11-30
关键词:
Automobile DrivingBioinformaticsBiological ProcessBladderCancer EtiologyCancer PatientCandidate Disease GeneCellsCellular Indexing of Transcriptomes and Epitopes by SequencingCessation of lifeClinicalCollectionComplexData SetDevelopmentDiagnosisDiseaseDistantExploratory/Developmental GrantFutureGene ExpressionGene Expression ProfileGenesGenetic TranscriptionGenomicsHeterogeneityHumanImmuneIndividualInvadedLeadMalignant neoplasm of urinary bladderMicrodissectionMolecularMolecular ProfilingMuscleMutationOperative Surgical ProceduresPatientsPopulationProcessPublic HealthPublishingRegulator GenesRelapseResearchSamplingSuspensionsTumor Cell InvasionTumor-infiltrating immune cellsbiomarker developmentbiomarker identificationcancer cellcell stromacell typegene networkimprovedinsightmuscle invasive bladder cancerneoplastic cellnew therapeutic targetpotential biomarkerpredictive markerprogramssingle-cell RNA sequencingtranscriptometranscriptome sequencingtranscriptomicstumor
中文摘要
项目摘要
肿瘤侵袭到膀胱粘膜下肌肉的存在定义了从
非致命性膀胱癌;然而,这一过程在分子水平上还没有被很好地理解。基因组学
肌肉浸润性膀胱癌(MIBC)的转录图谱最近发现了突变和基因
与已建立的MIBC相关的表达谱。尽管膀胱癌的一个重大进展
菲尔德,这些分析无法确定在单个肿瘤中激活的独特转录程序,
MIBC侵袭界面的间质和免疫群体。这主要是由于
准确收集浸润性肿瘤及其邻近/混合间质和浸润性免疫细胞的空间信息。AS
因此,早期的转录研究,甚至最近使用单细胞RNAseq的研究都依赖于异质性
实体瘤,包括非侵袭性和正常间质以及空间距离较远的免疫成分
从入侵的边界。这种异质性使得精确地去卷曲基因表达变得困难
肿瘤细胞、间质和浸润性免疫细胞所特有的征象
环境。我们假设不同的基因网络在单个肿瘤、间质和
MIBC侵袭性界面的免疫群体。RNAseq分析和生物信息学分析应该
揭示个体群体丰富而独特的转录特征。这项研究将
通过识别不同细胞群体的细胞和分子特征来产生积极影响
侵袭性进展。这些发现可能导致对候选基因网络的检查,这些网络将服务于
作为生物学功能的基础,识别潜在的生物标记物和需要的新的治疗靶点
适用于已被诊断为肌肉浸润性疾病或复发的膀胱癌患者。
英文摘要
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.
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科研奖励(0)
会议论文
Delineation of tumor, stromal and immune transcriptomes at the infiltrating interface of muscle invasive bladder cancer
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依托单位:
University of Michigan O'Brien Center for Urology Research
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批准号:7500607
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资助金额:$14.58万
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财政年份:2007
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依托单位:
University of Michigan O'Brien Center for Urology Research
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批准号:7500605
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资助金额:$3.37万
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财政年份:2007
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依托单位:
Rb/E2F in Hormone signaling of Prostate Epithelium
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资助金额:$22.0万
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依托单位:
Rb/E2F in Hormone signaling of Prostate Epithelium
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资助金额:$22.66万
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财政年份:2004
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负责人:MARK L DAY
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依托单位:
Rb/E2F in Hormone Signaling of Prostate Epithelium
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Role of Retinoblastoma in Prostate Homeostasis
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财政年份:2003
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依托单位:
University of Michigan O'Brien Center for Urology Res.
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资助金额:$65.47万
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依托单位:
University of Michigan O'Brien Center for Urology Res.
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项目类别:
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资助金额:$67.88万
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财政年份:2003
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负责人:MARK L DAY
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依托单位:
Role of Retinoblastoma in Prostate Homeostasis
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资助金额:$26.19万
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财政年份:2003
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负责人:MARK L DAY
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依托单位:
University of Michigan O'Brien Center for Urology Res.
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资助金额:$63.57万
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依托单位:
Role of Retinoblastoma in Prostate Homeostasis
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资助金额:$25.55万
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依托单位:
University of Michigan O'Brien Center for Urology Res.
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项目类别:
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资助金额:$67.88万
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University of Michigan O'Brien Center for Urology Res.
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资助金额:$67.88万
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财政年份:2003
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Role of Retinoblastoma in Prostate Homeostasis
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依托单位:
海外基金