Glycans in Hepatocellular Carcinoma

描述（由申请人提供）：早期发现癌症和癌前病变可提高患者生存率。本研究将确定与肝细胞癌发生相关的蛋白相关聚糖的变化。为了实现这一目标，我们开发了从血清蛋白中酶促去除的全甲基化聚糖的质谱分析。该方法允许对聚糖进行高效和高通量的比较。我们测试了一组试点的肝细胞癌病例和控制我们独特的研究，在埃及，一个国家的丙型肝炎病毒感染流行的肝细胞癌的方法。初步研究确定了三种聚糖，与慢性肝病对照组相比，预测肝细胞癌的准确率为90%。在这项研究中，我们建议扩大该项目，包括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进展为肝细胞癌过程中的聚糖变化，我们将继续改进聚糖定量和结构表征的分析方法。预计聚糖的定量将提高目前可用的肝细胞癌早期检测方法的性能。定义早期癌症的临床适用标志物对疾病管理和患者健康具有潜在的深远影响。聚糖标记物可用于筛查高危人群的早期疾病体征;设计和测试新的化学预防策略;以及在治疗后跟踪疾病进展。与疾病进展相关的聚糖变化的鉴定预计将产生新的肝癌发生假说。公共卫生相关性：早期发现癌症和癌前病变可提高患者生存率。这项研究将确定伴随肝癌发展的各种蛋白质装饰糖的变化。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。确定的糖可用于筛查肝癌早期症状的高危人群;设计和测试新的化学预防策略;并在治疗后跟踪疾病进展。

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.