Critical evaluation of LPCs markers for colorectal cancer

描述(申请人提供)：结直肠癌(CRC)是美国第三种最常见的癌症，也是与癌症相关的死亡的第二大原因。早期发现结直肠癌，5年相对生存率为90%。然而，只有37%的结直肠癌病例在早期被发现，而出现远处转移的受试者的5年存活率只有8-9%。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。尽管近年来发展了许多基于血液或粪便的结直肠癌检查，但这些检查都没有与结肠镜检查类似的敏感性和特异性。因此，仍然需要开发一种简单、非侵入性和高度可靠的早期检测CRC的方法。我们发现血浆中几种溶血磷脂酰胆碱(LPCS)水平是CRC的潜在标志物，在我们的试点工作中，这些标志物对CRC的敏感度和特异度分别达到82%和93%。为了严格评估这些标记物的临床意义和实用性，在完全独立的样本集中建立重复性，并重新测试和验证灵敏度和特异度的估计是至关重要的，也是绝对必要的。此外，确定LPCs在腺瘤性息肉中是否发生改变也很重要。我们提出了两个目标。首先，我们将在一项完全独立的研究中通过确定LPCS的敏感性和特异性来确定LPCS是否为检测CRC的有效标记物。对174对结直肠癌患者和结肠镜检查阴性对照的血样进行分析。其次，Will将确定血浆LPCS水平是否为早期结直肠肿瘤和/或疾病进展的标志。我们将确定与结肠镜检查阴性的健康对照组相比，腺瘤性息肉受试者(194例)血浆LPCS是否降低，以及LPCS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LPCS的临床应用潜力提供关键信息。公共卫生相关性：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。仍然需要开发一种简单、非侵入性和高度可靠的检测来早期发现CRC，因为当CRC在早期阶段被诊断出来时，它是可以治愈的。我们发现一组称为溶血磷脂酰胆碱(LPCS)的脂类化合物可能是早期发现结直肠癌的有用标记物。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对这些标记物进行批判性评估和验证。

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.