Novel Serum Markers for Pancreatic Adenocarcinoma

描述(申请人提供)：胰腺癌是导致美国男性和女性癌症死亡的第五大常见原因。5年生存率约为4%，是所有癌症中最低的。蛋白质组学研究的最新进展导致了血液中循环的疾病相关蛋白质的发现。这种蛋白质可能为检测和监测癌症提供了一种非侵入性的手段。由于目前可用的标记物临床应用有限，需要新的胰腺癌生物标记物。最广泛使用的胰腺肿瘤标记物CA19-9具有很高的变异性，在小肿瘤患者的血清中往往检测不到。已经在各种癌症患者和胰腺癌小鼠模型的血清中检测到两种蛋白质，结合珠蛋白和血清淀粉样蛋白A。然而，这些蛋白质在患有胰腺癌的人类中还没有得到充分的评估。本项目的目的是探讨结合珠蛋白和血清淀粉样蛋白A检测胰腺癌的潜在临床应用价值。具体地说，我们打算确定这些蛋白的血清水平在经病理证实的疾病患者中是否显著升高，确定血清水平是否与肿瘤严重程度的测量相关，并评估结合珠蛋白、血清淀粉样蛋白A和CA19-9在区分胰腺癌患者与年龄和性别匹配的对照组方面的相对准确性。在这项研究的第二阶段，我们将使用血清结合珠蛋白和血清淀粉样蛋白A的水平来评估通过犹他州人口数据库确定为胰腺癌高危家庭的成员。这项工作在确定改进的胰腺癌筛查试验方面具有直接的健康相关意义。

DESCRIPTION (provided by applicant): Adenocarcinoma of the pancreas is the fifth most common cause of cancer deaths in both men and women in the United States. The 5-year survival rate is about 4%, which is the lowest of any cancer. Recent advances in proteomic research have led to the discovery of disease-related proteins that circulate in the blood. Such proteins may provide a non-invasive means for detecting and monitoring cancer. Novel biomarkers for pancreatic adenocarcinoma are needed since currently available markers have limited clinical utility. The most widely used pancreatic tumor marker, CA 19-9, has high variability and is often undetectable in serum of patients with small tumors. Two proteins, haptoglobin and serum amyloid A, have been detected in the serum of patients with various cancers as well as a mouse model of pancreatic cancer. However, these proteins have not been adequately evaluated in humans with pancreatic adenocarcinoma. The goal of this project is to investigate the potential clinical utility of haptoglobin and serum amyloid A for detecting pancreatic adenocarcinoma. Specifically, we intend to determine if serum levels of these proteins are significantly elevated in patients with pathologically verified disease, determine if serum levels correlate with measures of tumor severity, and assess the relative accuracy for haptoglobin, serum amyloid A and CA 19-9 in distinguishing those patients with pancreatic adenocarcinoma from age and gender matched controls. In this study's second phase, we will use serum levels of haptoglobin and serum amyloid A to evaluate members of families identified through the Utah Population Database to be at high risk for pancreatic cancer. This work has direct health-related significance in identifying improved screening tests for pancreatic cancer.