Lysophosphatidylcholine Isoforms as Clinical Markers of Colorectal Cancer and Pol

描述(由申请人提供)： 项目摘要/摘要在美国，结直肠癌(CRC)是第三种最常见的癌症，也是癌症相关死亡的第二大原因。由于早期发现结直肠癌与良好的存活率相关，因此对于退伍军人来说，开发一种无创的、高度可靠的结直肠癌检测方法是非常必要的。虽然结肠镜检查报告的灵敏度和特异度超过95%，但由于费用以及与这项测试相关的不便和不适，坚持程度较低。因此，许多患者仍然患有晚期和潜在的致命疾病。我们发现血浆中几种称为溶血磷脂酰胆碱(LPCS)的脂质水平是CRC的潜在标记物，我们的前期工作表明这些标记物对CRC的敏感性和特异性分别为82%和93%。在完全独立的VA人群中建立重复性，并重新测试和验证敏感性和特异性的估计是至关重要的，也是绝对必要的，以便批判性地评估这些标记物的临床意义和实用性，以便对退伍军人有用。我们提出了两个目标。首先，我们将通过在完全独立的研究人群-VA患者群体中确定其敏感性和特异性，来严格评估血浆LPC水平是否是检测CRC的有效标志物。其次，我们将确定血浆LPC水平是否是癌前病变结肠息肉的有效标志物。我们的长期目标是1)开发高度敏感和可靠的诊断和预后、非或微创生物标记物，以改进对获得的结直肠癌患者样本的早期检测、管理和随访；2)开发生物标记物来检测癌前病变结肠息肉。对退伍军人医疗保健的潜在影响：退伍军人管理局(VA)诊断和/或治疗更多退伍军人患有结直肠癌，这种结直肠癌发病率将随着退伍军人管理局人口老龄化而增加。这项研究将为退伍军人提供一种重要的无创性诊断工具，以提高结直肠癌和结肠息肉的早期发现，从而优化退伍军人结直肠癌的医疗保健。 公共卫生相关性： 对退伍军人医疗保健的潜在影响：退伍军人管理局(VA)诊断和/或治疗更多退伍军人患有结直肠癌，这种结直肠癌发病率将随着退伍军人管理局人口老龄化而增加。这项研究将为退伍军人提供一种重要的无创性诊断工具，以提高结直肠癌和结肠息肉的早期发现，从而优化退伍军人结直肠癌的医疗保健。

DESCRIPTION (provided by applicant): Project Summary/Abstract Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the United States. Since early detection of CRC is associated with excellent survival rates, development of non- invasive and highly reliable test for CRC is greatly needed for veterans. While colonoscopy has reported sensitivity and specificity values exceeding 95%, the degree of adherence is low due to the cost, as well as to perceived inconvenience and discomfort associated with this test. As a result, many patients still present with late-stage and potentially fatal disease. We have found that plasma levels of several lipids, called lysophosphatidylcholines (LPCs), are potential markers for CRC and our pilot work show that these markers achieved a sensitivity and specificity of 82% and 93%, respectively for CRC. It is critical and absolutely necessary to establish reproducibility and to retest and validate the estimates for sensitivity and specificity in completely independent VA population sets in order to critically evaluate the clinical significance and utility of these markers to be useful for veterans. We propose 2 aims. First, we will critically evaluate whether plasma LPC levels are effective markers for detecting CRC by determining their sensitivity and specificity in VA patient population, a totally independent study population. Secondly, we will determine whether plasma LPC levels are effective markers for pre-cancerous adenomatous colon polyps. Our long-term goals are 1) to develop highly sensitive and reliable diagnostic and prognostic, non- or minimally invasive biomarkers for improving early detection, management and follow up of CRC patient samples obtained and 2) to develop biomarkers to detect pre-cancerous adenomatous colon polyps. Potential Impact on Veterans Health Care: More veterans are diagnosed and/or treated for colorectal cancer in the Veteran Administration (VA) and such CRC incidence rate will increase with aging VA population. The proposed research will provide an important diagnostic non-invasive tool for veterans to improve early detection of CRC and colon polyp thus optimize CRC medical care for VA population. PUBLIC HEALTH RELEVANCE: Potential Impact on Veterans Health Care: More veterans are diagnosed and/or treated for colorectal cancer in the Veteran Administration (VA) and such CRC incidence rate will increase with aging VA population. The proposed research will provide an important diagnostic non-invasive tool for veterans to improve early detection of CRC and colon polyp thus optimize CRC medical care for VA population.