Spectral Markers for Early Detection of Colon Neoplasia

用于早期检测结肠肿瘤的光谱标记

• 批准号: 6848173
• 负责人: Hemant K. Roy
• 金额: $ 36.77万
• 依托单位: NORTHSHORE UNIVERSITY HEALTHSYSTEM
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-27 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6848173
• 关键词: biomarker; biotechnology; cancer prevention; cancer risk; cell morphology; clinical research; colorectal neoplasms; computer data analysis; cooperative study; diagnosis design /evaluation; diagnosis quality /standard; early diagnosis; endoscopy; fiber optics; gene mutation; human genetic material tag; light scattering; molecular probes; nanotechnology; neoplasm /cancer genetics; polymerase chain reaction; prognosis; statistics /biometry

DESCRIPTION (provided by applicant): While colonoscopy is proven to decrease colorectal cancer (CRC) fatalities, its expense, complications and limited availability makes it impractical for general population screening. Risk-stratification through assessment of the "field effect" of colon carcinogenesis can be used to determine the need for colonoscopy; however current markers (e.g. distal colonic adenomatous polyp) are clearly inadequate. Dr. Backman's group and colleagues, having pioneered light-scattering technologies for detecting dysplastic cells (Nature 2000 & Nature Med 2001), now have developed four-dimensional light-scattering fingerprinting (4D-ELF), which enables quantitative analysis of nano-scale cellular architecture. Using 4D-ELF, we discovered spectral markers in histologically normal mucosa that preceded all conventional biomarkers of experimental CRC (Gastroenterology 2004). Evaluating 4D-ELF signatures from the uninvolved rectal mucosa had unprecedented sensitivity and positive predictive value (>98%) for the future occurrence of neoplasia. Pilot human studies confirmed the promise of these novel biomarkers. We propose to further validate these spectral markers by using an endoscopically-compatible 4D-ELF probe during colonoscopy. Based on rectal 4D-ELF analysis from 500 patients, we will formulate prediction rules for both the occurrence of advanced polyps/cancers and the exclusion of neoplasia (thus identifying a subgroup not requiring further screening). We will prospectively test these rules in 750 patients. Furthermore, we will use hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis as a paradigm to investigate whether the unparalleled sensitivity of 4D-ELF may detect long-term CRC risks engendered by an inherited predisposition. We will evaluate the ability of spectral marker to both identify mutations and forecast phenotypic presentation. In the future these spectral markers may be assayed with a 4D-ELF probe during rectal examination, thus providing a practical and accurate means of determining the optimal CRC screening regimen.

描述（由申请人提供）：虽然结肠镜检查被证明可减少结直肠癌（CRC）的死亡，但其费用，并发症和有限的可用性使得对一般人口筛查不切实际。 通过评估结肠癌的“现场效应”，可以使用风险分层来确定对结肠镜检查的需求。但是，当前的标记（例如远端结肠腺瘤息肉）显然不足。 Backman博士的小组及其同事具有开创性的光散射技术，用于检测异型细胞（Nature 2000＆Nature Med 2001），现在已经开发了四维光散射指纹（4D-ELF），可以对纳米尺度细胞结构进行定量分析。 使用4D-FEL，我们在组织学正常的粘膜中发现了光谱标记，该粘膜在实验性CRC的所有常规生物标志物之前（Gastroteerology 2004）。 评估未参与直肠粘膜的4D-elf特征具有前所未有的灵敏度和阳性预测价值（> 98％），以使肿瘤的未来发生。 飞行员人类研究证实了这些新型生物标志物的希望。 我们建议通过在结肠镜检查过程中使用内镜兼容的4D-ELF探针进一步验证这些光谱标记。 基于500名患者的直肠4D-ELF分析，我们将针对发生晚期息肉/癌症的出现和排除肿瘤的预测规则（从而确定了不需要进一步筛查的亚组）。 我们将在750名患者中前瞻性测试这些规则。 此外，我们将使用遗传性非型型结直肠癌和家族性腺瘤性息肉病作为范式，以研究4D-ELF的无与伦比的灵敏度是否可以检测到由遗传易感性产生的长期CRC风险。 我们将评估光谱标记既鉴定突变和预测表型表现的能力。 将来，这些光谱标记物可以在直肠检查过程中用4D-FELT探针测定，从而提供了确定最佳CRC筛选方案的实用和准确方法。