Precision Interception of Gastric Cancer Precursors Through Molecular and Cellular Risk Stratification

通过分子和细胞风险分层精准拦截胃癌前体

基本信息

批准号：
10715761
负责人：
JOO HA HWANG
金额：
$ 180.3万
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/10715761
关键词：
Address Administrative Coordination Affect American Attenuated Bacteria Basic Science Biological Markers Biological Specimen Banks Biology Biometry Cancer Biology Cancer Diagnostics Cancer Etiology Chile Clinical Clinical Data Clinical Research Clinical Trials Communicable Diseases Communication Data Data Analyses Detection Development Diagnosis Early Diagnosis Ensure Epithelial Cells Epithelium Experimental Models Foundations Gastric Adenocarcinoma Gastroenterology Genome Genomics Goals Health Expenditures Helicobacter Infections Helicobacter pylori Image Individual Infection Inflammatory Intercept Interdisciplinary Study Lesion Longterm Follow-up Malignant Neoplasms Methods Modeling Molecular Molecular Analysis Morbidity - disease rate Occupational activity of managing finances Oncology Outcome Patients Persons Precancerous Conditions Preneoplastic Change Prevention Prevention strategy Program Research Project Grants Public Health Research Resources Risk Risk Factors Sampling Screening for Gastric Cancer Screening for cancer Stomach Translational Research United States Universities antimicrobial attenuation biomarker discovery biomarker identification cancer diagnosis cancer prevention cancer risk carcinogenesis clinical care clinical practice clinically relevant cohort data management epidemiology study gastric cancer prevention gastric carcinogenesis gastric intestinal metaplasia gastrointestinal genetic analysis genomic data high risk improved insight interdisciplinary approach malignant stomach neoplasm medical specialties mortality neoplasm registry novel novel strategies patient subsets precision cancer prevention precision medicine premalignant programs risk stratification single cell sequencing stem cell niche synergism tumor progression

项目摘要

ABSTRACT – OVERALL Gastric cancer is a leading cause of cancer morbidity and mortality worldwide. The bacterium Helicobacter pylori (Hp) is the single greatest risk factor for gastric cancer, its infection triggering an inflammatory cascade within the gastric microenvironment. Many people infected with Hp develop a precancerous lesion called gastric intestinal metaplasia (GIM), and while some are minimally affected by the condition, others go on to develop invasive gastric cancer. There remain many unanswered questions about how Hp interacts with the gastric microenvironment and promotes gastric cancer, and why GIM poses variable risk to patients. The focus of this Program Project Grant (PPG) is characterizing the molecular and genomic features of gastric epithelial cells in high-risk versus low-risk gastric precancerous lesions, with Hp as a stratifying risk factor. The PPG involves three distinct yet synergistic projects: (1) Molecular and Cellular Determinant of High-Risk Gastric Precancerous Lesions. (2) Ex Vivo Modeling of Gastric Precancerous Lesions. (3) Molecular Risk Stratification of Gastric Precancerous Lesions. The leaders of the PPG’s multidisciplinary research teams have backgrounds in the relevant clinical specialties of infectious disease, gastroenterology and gastrointestinal oncology. The PPG leverages broad and deep research expertise in single-cell sequencing, Hp biology, epidemiology and clinical research for gastric cancer prevention. There are several robust and synergistic clinical cohorts and biospecimen repositories that make up the foundation of the PPG. These include two cohorts of gastric precancerous lesions, the Gastric Precancerous Conditions Study (GAPS, Stanford University) and the NCI-supported Gastric Cancer Precursor Lesions Study (GPCL, Pontificia Universidad Católica de Chile), the Gastric Cancer Registry (GCR, Stanford University), and the NCI-supported Hp Genome Project (HpGP, Vanderbilt University). The translational and clinical projects in the PPG offer a novel strategy of high-impact precision interception and cancer prevention to reduce gastric cancer risk. The interdisciplinary approach in this PPG is essential for improving clinical prevention strategies and risk attenuation of gastric cancer.

摘要 - 总体胃癌是全球癌症发病率和死亡率的主要原因。细菌幽门螺杆菌（HP）是胃癌的最大危险因素，其感染引发了炎症性级联胃微环境。许多感染HP的人会发展出一种癌性病变，称为胃肠道化生（gim），虽然有些人受到这种疾病的影响，但其他人则继续发展侵入性胃癌。关于HP如何与胃互动，还有许多未解决的问题微环境并促进胃癌，以及为什么GIM对患者具有可变的风险。重点计划项目赠款（PPG）表征胃上皮细胞的分子和基因组特征高风险与低风险胃癌性病变，HP是分层的危险因素。 PPG涉及三个独特但协同的项目：（1）高危胃癌病变的分子和细胞决定因素。（2）胃癌性病变的体内建模。（3）胃癌病变的分子风险分层。 PPG的多学科研究团队的领导者在相关的临床专业中具有背景传染病，胃肠病学和胃肠道肿瘤学。 PPG利用广泛而深胃癌单细胞测序，HP生物学，流行病学和临床研究方面的研究专业知识预防。有几个强大的和协同的临床人群和生物循环库，可以构成 PPG的基础。其中包括两个胃癌性病变，胃癌条件研究（Stanford University GAPS）和NCI支持的胃癌前体病变研究（GPCL，Pontificia大学Católicade Chile），胃癌登记处（GCR，斯坦福大学）和 NCI支持的HP基因组项目（HPGP，范德比尔特大学）。转化和临床项目 PPG提供了一种新型的高冲击精度截距和预防癌症的策略，以减少胃癌症风险。该PPG中的跨学科方法对于改善临床预防策略至关重要和胃癌衰减的风险。