Glycans in Hepatocellular Carcinoma

描述(由申请人提供)：及早发现癌症和癌前状态可提高患者存活率。这项研究将确定与肝细胞癌发展相关的蛋白相关糖链的变化。为了实现这一目标，我们开发了酶法从血清蛋白中去除的过甲基化多聚糖的质谱分析。这种方法允许高效和高通量地比较多聚糖。我们在埃及的一组实验性肝细胞癌病例和对照上测试了这种方法，这些病例和对照来自我们对埃及的独特研究，埃及是一个丙型肝炎病毒感染流行的国家。这项先导性研究确定了三种预测肝细胞癌的多糖，与慢性肝病对照组相比，预测准确率为90%。在这项研究中，我们建议扩大该项目，并纳入美国人群中肝细胞癌病例和慢性肝病对照的比较。随着我们继续评估慢性病毒感染发展为肝细胞癌过程中的糖链变化，我们将继续改进糖链的定量和结构表征的分析方法。预计葡聚糖的量化将改善目前可用于肝细胞癌早期检测的方法的性能。定义临床适用的早期癌症标志物对疾病管理和患者健康具有潜在的深远影响。这些葡聚糖标记物可用于筛选高危人群的早期疾病迹象，设计和测试新的化学预防策略，以及跟踪治疗后的疾病进展。确定与疾病进展相关的糖链变化有望为肝脏癌变产生新的假说。公共卫生相关性：癌症和癌前状态的早期检测提高了患者的存活率。这项研究将确定伴随着肝癌发展的各种蛋白质修饰糖的变化。为了实现这一目标，我们开发了允许高通量比较这些糖的方法。识别出的糖可用于筛选肝癌早期迹象的高危人群；设计和测试新的化学预防策略；以及跟踪治疗后的疾病进展。

DESCRIPTION (provided by applicant): Early detection of cancer and precancerous conditions improves patient survival. This study will identify changes in protein associated glycans associated with the development of hepatocellular carcinoma. To achieve this goal, we developed mass spectrometric analysis of permethylated glycans enzymatically removed from serum proteins. This method allows an efficient and high-throughput comparison of glycans. We tested the method on a pilot set of hepatocellular carcinoma cases and controls from our unique study of hepatocellular carcinoma in Egypt, a country with an epidemic of hepatitis C viral infection. The pilot-study identified three glycans that predict hepatocellular carcinoma with 90% prediction accuracy compared to controls with chronic liver disease. In this study, we propose to expand the project and to include a comparison of hepatocellular carcinoma cases and chronic liver disease controls in the US population. As we continue to assess glycan changes in the progression of chronic viral infection to hepatocellular carcinoma, we will continue to improve the analytical methods for quantification and structural characterization of the glycans. It is expected that the quantification of glycans will improve the performance of currently available methods for early detection of hepatocellular carcinoma. Defining clinically applicable markers of early-stage cancer has potentially far-reaching consequences for disease management and patient health. The glycan markers could be used to screen high risk populations for early signs of disease; to design and test new chemoprevention strategies; and to follow disease progression after treatment. Identification of the changes in glycans associated with disease progression is expected to generate new hypotheses for carcinogenesis of the liver. PUBLIC HEALTH RELEVANCE: Early detection of cancer and precancerous conditions improves patient survival. This study will identify changes in various protein-decorating sugars that accompany the development of liver cancer. To achieve this goal, we developed methods that allow high-throughput comparison of these sugars. The identified sugars could be used to screen high risk populations for early signs of liver cancer; to design and test new chemoprevention strategies; and to follow disease progression after treatment.