Project 1 - Molecular and Cellular Determinants of High Risk Gastric Precancerous Lesions

项目1——高危胃癌癌前病变的分子和细胞决定因素

基本信息

批准号：
10715762
负责人：
Hanlee P Ji
金额：
$ 36.89万
依托单位：
STANFORD UNIVERSITY
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：
2023-09-20 至 2028-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10715762
关键词：
20q Age Anatomy Atrophic Bacteria Biology Cancer Detection Cancer Etiology Categories Cells Cellular biology Cessation of life Chromosome Arm Chromosome Mapping Chromosome abnormality Chronic Classification Clinical Correa cascade DNA Sequence Alteration Diagnosis Dysplasia Early Diagnosis Epigenetic Process Epithelial Cells Epithelium Event Gastric Tissue Gastritis Gene Expression Profile Gene Expression Profiling Genes Genetic Genomics Goals Health Helicobacter Infections Helicobacter pylori Helicobacter pylori induced gastric cancer Histologic Human Immunohistochemistry Individual Infection Inflammation Intestinal Metaplasia Intestines Lesion Lesion by Stage Link Location Methods Modeling Molecular Molecular Profiling Morbidity - disease rate Outcome Patients Pattern Population Precancerous Conditions Prevention Prevention strategy Process Property Proteins Risk Risk Assessment Risk Factors Sampling Somatic Mutation Specimen Staging Staging System Stomach Stomach Carcinoma Therapeutic Tissues Translating United States Work candidate marker clinical biomarkers clinical risk cohort detection method gastric intestinal metaplasia gastric organoids genomic aberrations high risk high risk population improved insight malignant stomach neoplasm mortality multi-ethnic multiple omics novel premalignant progression risk risk stratification sex stem cells transcriptome sequencing transcriptomics tumor progression

项目摘要

ABSTRACT – PROJECT 1 The main objective of Project 1 is to deconvolute the molecular features of high-risk gastric cancer precursor lesions. Dr. Hanlee Ji, Project Leader, previously found that the epithelium of early gastric cancer is characterized by distinct genomic, transcriptomic and cellular properties. In addition, the Ji Group has identified a distinct gene expression profile associated with high-risk precancerous gastric lesions compared to low-risk lesions and normal controls. Project 1 represents a continuation of this work with a specific focus on characterizing the genetic and molecular profile of precancerous gastric tissue. There are two specific aims to this project: (1) Identify the specific gene expression signatures associated with high-risk gastric intestinal metaplasia (GIM). (2) Characterize aberrant epithelial cells and their subtypes in high-risk gastric cancer precursors. In Aim 1, Dr. Ji will employ bulk RNA sequencing and spatial transcriptomics to study GIM lesions that range across the spectrum of neoplastic progression. Hp infection status will be used as a stratifying risk factor. These results will identify the molecular profile associated with the highest risk of progression to gastric cancer and Hp- associated alterations in stomach cells. Aim 2 will use single cell multi-omics to identify the subset of GIM epithelial cells with somatic mutations, copy number alterations and epigenetic patterns that are associate with gastric cancer. The results will determine the genetic and genomic features of epithelial cells that comprise high- risk precancerous lesions in the stomach. Ultimately, this project will elucidate the precise molecular and cellular features associated with high-risk GIM to gain novel insight into the molecular, cellular and genomic factors that contribute to a high-risk premalignant state.

摘要 – 项目 1 项目1的主要目标是解析高危胃癌前驱物的分子特征项目负责人 Hanlee Ji 博士此前发现早期胃癌的上皮有特征。此外，季氏研究组还鉴定出了一个独特的基因。与低风险病变相比，与高风险癌前病变相关的表达谱项目 1 是这项工作的延续，特别关注表征该项目有两个具体目标： (1) 鉴定与高危胃肠化生相关的特定基因表达特征（GIM）。 (2) 描述高危胃癌前体中异常上皮细胞及其亚型的特征。在目标 1 中，季博士将采用批量 RNA 测序和空间转录组学来研究范围广泛的 GIM 病变整个肿瘤进展范围内的 Hp 感染状态将被用作分层危险因素。结果将确定与进展为胃癌和 Hp 的最高风险相关的分子特征目标 2 将使用单细胞多组学来识别 GIM 的子集。具有体细胞突变、拷贝数改变和表观遗传模式的上皮细胞与结果将确定构成高表达的上皮细胞的遗传和基因组特征。最终，该项目将阐明精确的分子和细胞因素。与高风险 GIM 相关的特征，以获得对分子、细胞和基因组因素的新见解导致高风险的癌前状态。