Serum biomarkers for early detection of H. pylori-associated gastric cancer

用于早期检测幽门螺杆菌相关胃癌的血清生物标志物

• 批准号: 8107435
• 负责人: JAY V. SOLNICK
• 金额: $ 29.78万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-21 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8107435
• 关键词: Aging; Area; Atrophic Gastritis; Award; Biological Assay; Biological Markers; Biology; Cancer Etiology; Cancerous; Carcinogens; Cessation of life; Characteristics; Chronic; Cities; Clinical Pathways; Collaborations; Colombia; Computing Methodologies; Data; Detection; Developed Countries; Developing Countries; Development; Diagnostic Neoplasm Staging; Diet; Disease; Dysplasia; Early Diagnosis; Early treatment; Enrollment; Environmental Risk Factor; Event; Gastric Adenocarcinoma; Gastritis; Genetic; Glycoproteins; Health; Helicobacter Infections; Helicobacter pylori; Histologic; Histology; Histopathology; Immunoassay; Individual; Inflammation; Inflammatory Response; Intervention; Intestinal Metaplasia; Intestines; Latin America; Lesion; Link; Malignant Neoplasms; Marshal; Mass Spectrum Analysis; Measures; Medicine; Mexico; Mucins; Nobel Prize; Non-Invasive Cancer Detection; Oligosaccharides; Pathologic; Pathology; Patients; Pattern; Peptic Ulcer; Physiology; Polysaccharides; Population; Premalignant; Prevalence; Prevention strategy; Proteins; Research; Research Personnel; Risk; Sampling; Second Primary Cancers; Series; Serum; Sodium Chloride; Staging; Stomach; Tissues; United States; Universities; base; cohort; fruits and vegetables; glycosylation; killings; malignant stomach neoplasm; mortality; professor; social

DESCRIPTION (provided by applicant): Gastric cancer is the fourth most common cancer and the second most common cause of cancer death worldwide, killing nearly 700,000 people each year. The most common histology is the intestinal (well-differentiated) type, which follows a temporal sequence of pathologic changes that leads from chronic non-atrophic gastritis, to atrophic gastritis, intestinal metaplasia, dysplasia, and finally gastric adenocarcinoma. Environmental factors such as excessive dietary salt and lack of fresh fruits and vegetables were long suspected to be the inciting event that initiated the gastric inflammatory response. However, our understanding of gastric cancer underwent a dramatic change with the discovery of Helicobacter pylori in 1982 by Marshall and Warren, who in 2005 were awarded the Nobel Prize in Physiology or Medicine. Approximately half the world's population is infected with H. pylori, with prevalence reaching more than 80% in many developing countries. While diet and host genetics continue to be recognized as important determinants of gastric cancer, approximately 60% of gastric cancer is attributable to H. pylori infection, prompting the designation of H. pylori as a carcinogen by the WHO. Early detection and preventive strategies offer the best opportunity to decrease mortality from gastric cancer, which is most commonly detected at stage III or IV where 5- year survival is only 3-13%. Identification of serum biomarkers for the histologic stages leading to gastric cancer offers the possibility for non-invasive detection of those H. pylori-infected patients who are most at risk for development of cancer. We hypothesize that a panel of protein or glycosylation biomarkers can be measured in serum that will permit early detection of precancerous lesions and guide intervention before the development of late stage cancer. We propose four Specific Aims: (1) Establish sets of serum samples from groups of patients with well-characterized precancerous or cancerous gastric histopathology; (2) Perform quantitative detection of protein biomarkers in serum of patients with well-characterized gastric histopathology using flow cytometric, multiplex immunoassays; (3) Perform mass spectrometry to identify oligosaccharide markers in serum from patients with well- characterized precancerous or cancerous gastric histopathology; and (4) Purify mucin glycoproteins from serum of patients with well-characterize gastric histopathology, and analyze O-linked glycans by MS. PUBLIC HEALTH RELEVANCE: Helicobacter pylori-associated gastric cancer is the second most common cause of cancer death in the world. We propose to identify serum biomarkers of gastric cancer and its precursor lesions that would permit early detection and intervention before the disease has progressed to an advanced stage where it is rarely curable.

描述（由申请人提供）：胃癌是全球第四大常见癌症和第二大常见癌症死亡原因，每年造成近70万人死亡。最常见的组织学类型是肠型（分化良好），其病理变化遵循从慢性非萎缩性胃炎到萎缩性胃炎、肠上皮化生、异型增生和最后胃腺癌的时间顺序。环境因素，如过量的饮食盐和缺乏新鲜水果和蔬菜，长期以来一直被怀疑是引发胃炎反应的煽动事件。然而，随着马歇尔和沃伦在1982年发现幽门螺杆菌，我们对胃癌的认识发生了巨大的变化，他们在2005年获得了诺贝尔生理学或医学奖。世界上大约有一半的人口感染了H。幽门螺杆菌，在许多发展中国家的患病率达到80%以上。虽然饮食和宿主遗传学仍然被认为是胃癌的重要决定因素，但大约60%的胃癌可归因于H。pylori感染，促使命名为H.幽门螺杆菌作为一种致癌物质由世界卫生组织。早期发现和预防策略提供了降低胃癌死亡率的最佳机会，胃癌最常在III或IV期发现，5年生存率仅为3- 13%。识别导致胃癌的组织学阶段的血清生物标志物为非侵入性检测那些H。幽门螺杆菌感染的患者是最有可能发展成癌症的。我们假设可以在血清中测量一组蛋白质或糖基化生物标志物，这将允许早期检测癌前病变并在晚期癌症发展之前指导干预。我们提出四个具体目标：（2）使用流式细胞术、多重免疫测定对具有良好特征的胃组织病理学的患者的血清中的蛋白质生物标志物进行定量检测;（3）进行质谱分析，以鉴定来自具有良好免疫功能的患者的血清中的寡糖标志物。表征的癌前或癌性胃组织病理学;和（4）从具有良好表征的胃组织病理学的患者的血清中纯化粘蛋白糖蛋白，并通过MS分析O-连接聚糖。幽门螺杆菌相关性胃癌是世界上第二大常见的癌症死亡原因。我们建议确定胃癌及其前体病变的血清生物标志物，以便在疾病进展到难以治愈的晚期之前进行早期检测和干预。