Serum Biomarkers for Colorectal Cancer Detection

描述(申请人提供)：当癌症在最早阶段被发现时，癌症存活率显著增加，因此能够发现早期癌症的诊断筛查测试是至关重要的。我们研究的总体目标是开发这样一种早期检测筛查测试。我们打算前瞻性地积累大量明确的结直肠癌(CRC)病例，我们在诊断时收集关于这一队列的广泛数据。我们将生成一个全面的数据库，其中包括人口统计学、个人和家族史、肿瘤特征和合并症等数据。我们的初步研究工作是利用我们发现的结直肠癌患者和健康对照组的血清开发一种检测方法。我们开发了一种高通量的方法来分离抗原的cDNA克隆，这种方法可以通过检测受试者血清中是否存在抗肿瘤蛋白的自身抗体来识别癌症病例。我们的第一个目标是利用我们最初发现的队列，识别在区分结直肠癌患者和健康对照血清中至关重要的最少数量的抗原克隆。我们将从我们发现的3800个克隆中剔除抗原克隆，这些克隆与其他癌症、良性胃肠道疾病、复制或不与任何CRC血清反应的患者的血清发生反应。我们的第二个目标是确定这些新选择的抗原标记物的测试特征(敏感性、特异性、准确性)，以使用新获得的血清样本来区分结直肠癌病例，这些血清样本以前没有在标记物集的开发中使用。最后，我们打算确定这些抗原标记物在一大群独立的、明确界定的结直肠癌患者和健康对照人群中的测试特征。此外，由于研究人群的大小、种族/民族构成以及捕获的患者数据，我们将能够评估这些标记物与重要亚组的关系。

DESCRIPTION (provided by applicant): When cancer is identified at the earliest stages, cancer survival rates dramatically increase and therefore diagnostic screening tests that can detect early stage cancer are crucial. The overall goal of our research is to develop such an early detection screening test. We intend to prospectively accrue a large well-defined independent cohort of colorectal cancer (CRC) cases where we collect extensive data on this cohort at the time of diagnosis. We will generate a comprehensive database that includes data on demographics, personal and family history, tumor characteristics, and comorbidities. Our preliminary research efforts have been to develop a detection assay utilizing the sera of our discovery cohort of CRC patients and healthy controls. We have developed a high throughput method to isolated cDNA clones of antigens which can be used to identify cancer cases by detecting the presence of auto-antibodies to tumor proteins in the serum of the test subject. Our first aim is to identify the minimal number of antigen clones that are critical in distinguishing sera from patients with colorectal cancer from healthy controls utilizing our initial discovery cohort. We will eliminate antigen clones from our discovery set of 3800 clones that react with sera from patients with other cancers, benign gastrointestinal conditions, duplicates or do not react with any CRC sera. Our second aim is to determine the test characteristics (sensitivity, specificity, accuracy) on these newly selected antigen markers for distinguishing colorectal cancer cases using newly acquired sera samples not previously used in the development of the marker set. Lastly, we intend to determine the test characteristics of these antigen markers on a large independent well-defined cohort of colorectal cancer patients and healthy controls. In addition, due to the size, racial/ethnic makeup of the study population, and captured patient data, we will be able to evaluate the expression of these markers in relationship to important subgroups.