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

摘要-项目1 项目1的主要目标是解开高危胃癌先兆的分子特征 损伤。项目负责人季汉礼博士此前发现，早期胃癌的上皮细胞具有 通过不同的基因组、转录和细胞特性。此外，纪万昌集团还发现了一种独特的基因 与低危病变和高危癌前病变相关的表达谱 正常对照组。项目1代表了这项工作的继续，具体侧重于描述 癌前病变组织的遗传学和分子生物学研究。这个项目有两个具体目标： (1)确定与高危胃肠化生相关的特定基因表达特征 (GIM)。 (2)研究高危胃癌前病变中异常上皮细胞及其亚型的特征。 在目标1中，季博士将使用批量RNA测序和空间转录切割技术来研究该范围内的牙周膜病变 横跨肿瘤进展的光谱。幽门螺杆菌感染状况将作为分层危险因素。这些 结果将确定与进展为胃癌和幽门螺杆菌最高风险相关的分子图谱。 胃细胞的相关改变。AIM 2将使用单细胞多组学来鉴定GIM亚集 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 胃癌。这一结果将决定上皮细胞的遗传和基因组特征，这些上皮细胞包括高密度脂蛋白。 胃部有癌前病变的风险。最终，这个项目将阐明精确的分子和细胞 与高危GIM相关的特征，以获得对分子、细胞和基因组因素的新见解 导致高危的癌前状态。

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.