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

• 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
• 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

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的主要目的是解宣告高危胃癌前体的分子特征 病变。项目负责人Hanlee Ji博士以前发现早期胃癌的上皮是特征的 通过不同的基因组，转录组和细胞特性。此外，JI组已经确定了一个独特的基因 与低风险病变相比 正常对照。项目1代表这项工作的延续，特别着眼于表征 癌前胃组织的遗传和分子谱。该项目有两个具体的目标： （1）确定与高风险胃肠化生相关的特定基因表达特征 （gim）。 （2）表征在高危胃癌前体中异常上皮细胞及其亚型。 在AIM 1中，JI博士将采用大量的RNA测序和空间转录组学来研究范围的GIM病变 跨越肿瘤进展的光谱。 HP感染状态将用作分层风险因素。这些 结果将确定与胃癌和HP-进展最高风险相关的分子特征 相关的变化滞后细胞。 AIM 2将使用单细胞多摩学来识别GIM的子集 具有躯体突变，拷贝数改变和表观遗传模式的上皮细胞与与之相关的表观遗传模式 胃癌。结果将确定上皮细胞的遗传和基因组特征 胃中的风险精度病变。最终，该项目将阐明精确的分子和细胞 与高风险GIM相关的特征，以获得对分子，细胞和基因组因子的新见解，这些因素 有助于高风险的前态状态。