Spatial Profiling of Melanocytic Tumors and Their Microenvironment
黑素细胞肿瘤及其微环境的空间分析
基本信息
- 批准号:10729434
- 负责人:
- 金额:$ 8万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AddressArchitectureBenignBiological MarkersBiological SciencesBiologyCDK2 geneCellsCellularityCharacteristicsChromosome MappingComplexCoupledCutaneous MelanomaCytokeratinDataDermisDevelopmentDiagnosisDiagnostic ErrorsEarly DiagnosisEndothelial CellsEpidermisEpithelial CellsFibroblastsGene CombinationsGene ExpressionGene Expression ProfileGene Expression ProfilingGenesGoalsImmuneImmunohistochemistryKnowledgeMART-1 Tumor AntigenMalignant - descriptorMalignant NeoplasmsMapsMelanocytic NeoplasmMelanocytic nevusMetastatic MelanomaMethodologyMole the mammalMorphologyNeoplasm MetastasisNeoplasmsNevi and MelanomasNevusPTPRC genePatient-Focused OutcomesPatternPeripheralPopulationRegulationResearchResolutionRoleSkin CancerSpace PerceptionStructureSurvival RateTestingTissuesTranscriptTumor BiologyTumor MarkersTumor Tissuebiomarker developmentbiomarker identificationcell typecellular imagingdiagnostic accuracydiagnostic biomarkerdiagnostic criteriadiagnostic valuedifferential expressiondigitalgene panelimaging platformimprovedinnovationkeratinocytemelanocytemelanomamelanoma biomarkersneoplastic cellnovel diagnosticsnovel markerpreservationpreventsingle cell sequencingsingle-cell RNA sequencingsuccesstranscriptometumortumor heterogeneitytumor microenvironmenttumor progressiontumor-immune system interactions
项目摘要
Spatial profiling of melanocytic tumors and their microenvironment
Understanding tissue structure is fundamental for biological sciences and for distinguishing benign versus
malignant neoplasms, but histopathological assessment alone is inaccurate for the diagnosis of certain tumors,
including a subset of melanocytic neoplasms (melanocytic nevi and melanomas), resulting in diagnostic errors
and worsened patient outcomes. Therefore, novel biomarkers for the diagnosis of melanoma are needed. To
identify such markers, it is imperative to better understand the interaction between melanocytes and neighboring
keratinocytes, immune cells, and other components of the complex tumor microenvironment in nevi and
melanoma.
Nevi and early primary melanoma display intratumoral heterogeneity, often coupled with low cellularity and purity.
Therefore, the tumor-microenvironment interactions could be missed by bulk approaches or single-cell
sequencing of advanced/metastatic tumors only, which has been the focus of most prior studies. The goal of this
research is to build high-resolution spatial maps of gene expression of the tumor and its microenvironment in
morphologically preserved nevi and melanomas to identify novel diagnostic biomarkers.
The hypothesis is that melanocytic tumors and their microenvironments contain subpopulations of cells with
characteristic gene expression patterns that differ between nevi and melanoma. We hypothesize that some of
these differentially expressed genes are spatially confined and cell-type specific and could be used as potential
diagnostic markers. Our prior data demonstrated differences in CDK2 gene expression between melanocyte-
rich regions of nevi and melanoma. In Aim 1, we will assess spatial expression of CDK2 by
immunohistochemistry in a tumor panel of over 200 nevi versus melanoma, comparing it to proliferative markers,
as well as established melanoma biomarkers, including PRAME. In Aim 2, to identify novel biomarkers, we will
establish high-resolution spatial maps of gene expression of tumor and microenvironment subpopulations in nevi
versus melanoma by performing a spatial whole transcriptome analysis and a high-plex single-cell imaging. Top
differentially expressed genes in these subpopulations will be validated via immunohistochemistry in the tumor
panel described above.
This study improves current theoretical concepts by investigating tumor and microenvironment populations in
nevi and early primary melanoma – the common, yet previously understudied tumor types. Furthermore, this
study utilizes improved state-of-the-art approaches, including high-plex single-cell spatial gene expression
profiling. This research will improve the understanding of tumor-microenvironment subpopulations in their
spatially correct context, relevant for tumor biology and biomarker development, ultimately leading to improved
diagnostic accuracy of melanoma and improved patient outcomes.
黑素细胞肿瘤的空间分布及其微环境
项目成果
期刊论文数量(0)
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Maija Helena Tuulia Kiuru其他文献
Maija Helena Tuulia Kiuru的其他文献
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