Critical evaluation of LPCs markers for colorectal cancer

描述（由申请人提供）：结直肠癌（CRC）是美国第三大最常诊断的癌症，也是癌症相关死亡的第二大原因。如果早期发现CRC，5年相对生存率为90%。然而，只有37%的CRC病例在早期阶段被检测到，并且存在远处转移的受试者的5年生存率仅为8- 9%。虽然结肠镜检查报告的灵敏度和特异性值超过95%，但由于成本以及与该测试相关的感知不便和不适，依从性程度较低。因此，许多患者仍然存在晚期和潜在致命的疾病。虽然近年来已经开发了许多基于血液或粪便的CRC测试，但这些测试都没有与结肠镜检查相似的灵敏度和特异性。因此，对于开发用于早期检测CRC的简单、非侵入性和高度可靠的测试仍然存在重要需求。我们发现，血浆中几种溶血磷脂酰胆碱（LPC）水平是CRC的潜在标志物，在我们的试点工作中，我们表明这些标志物对CRC的敏感性和特异性分别为82%和93%。建立重现性并在完全独立的样本集中重新测试和验证灵敏度和特异性的估计值，以便严格评估这些标志物的临床意义和实用性，这是至关重要且绝对必要的。此外，重要的是要确定是否LPCs在腺瘤性息肉的变化。我们提出两个目标。首先，我们将在一项完全独立的研究中通过确定LPC的敏感性和特异性来确定LPC是否是检测CRC的有效标志物。将分析来自CRC病例和结肠镜阴性对照的174对血液样本。其次，将确定LPC的血浆水平是否是早期结直肠肿瘤和/或疾病进展的标志物。我们将确定与结肠镜检查阴性的健康对照相比，腺瘤性息肉受试者（194个样本）的血浆LPC是否减少，以及LPC水平是否与腺瘤性息肉的大小和组织病理学相关。这些研究将为评估LPC临床应用的潜力提供关键信息。 公共卫生相关性：结直肠癌（CRC）是美国第三大最常见的癌症，也是癌症相关死亡的第二大原因。对于开发用于早期检测CRC的简单、非侵入性和高度可靠的测试仍然存在重要需求，因为当CRC在早期阶段被诊断时，它是可治愈的。我们发现一组称为溶血磷脂酰胆碱（LPC）的脂质化合物可能是早期检测CRC的有用标志物。拟议的研究将在健康对照受试者、腺瘤性息肉患者和结直肠癌患者中严格评估和验证这些标志物。

DESCRIPTION (provided by applicant): Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the United States. When CRC is detected early, the 5-year relative survival rate is 90%. However, only 37% of CRC cases are detected at an early stage and the 5-year survival rate for subjects presenting with distant metastases is only 8-9%. 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. Although many blood- or stool-based tests for CRC have been developed in recent years, none of these tests have sensitivity and specificity similar to those of colonoscopy. Thus, there continues to be an important need for the development of a simple, non-invasive and highly reliable test for the early detection of CRC. We have found that plasma levels of several lysophosphatidylcholines (LPCs) are potential markers for CRC and in our pilot work we 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 sample sets in order to critically evaluate the clinical significance and utility of these markers. In addition, it is important to determine whether LPCs are changed in adenomatous polyps. We propose two aims. First, we will determine whether LPCs are effective markers for detecting CRC by determining their sensitivity and specificity in a totally independent study. 174 pairs of blood samples from CRC cases and colonoscopic negative controls will be analyzed. Secondly, will will determine whether plasma levels of LPCs are markers for early colorectal neoplasia and/or disease progression. We will determine whether plasma LPCs are reduced in subjects with adenomatous polyps (194 samples), as compared to colonoscopically negative healthy controls, and whether the levels of LPCs correlate with the size and histo-pathology of adenomatous polyps. These studies will provide critical information to evaluate the potential of LPCs' clinical usage. PUBLIC HEALTH RELEVANCE: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths in the United States. There continues to be an important need for the development of a simple, non-invasive and highly reliable test for the early detection of CRC, since when CRC is diagnosed at an early stage, it is curable. We have found that a group of lipid compounds called lysophosphatidylcholines (LPCs) may represent useful markers for the early detection of CRC. The proposed studies will critically evaluate and validate these markers in healthy control subjects, patients with adenomatous polyps, and patients with colorectal cancers.