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）：虽然结肠镜检查已被证明可以减少结直肠癌 (CRC) 死亡率，但其费用、并发症和有限的可用性使其对于一般人群筛查来说不切实际。 通过评估结肠癌发生的“场效应”进行风险分层可用于确定是否需要进行结肠镜检查；然而，目前的标志物（例如远端结肠腺瘤性息肉）显然是不够的。 Backman 博士的团队和同事率先开发了用于检测发育不良细胞的光散射技术 (Nature 2000 & Nature Med 2001)，现在又开发出了四维光散射指纹识别 (4D-ELF)，可以对纳米级的细胞进行定量分析。细胞结构。 使用 4D-ELF，我们在组织学正常粘膜中发现了光谱标记，这些标记先于实验性 CRC 的所有传统生物标记（Gastroenterology 2004）。 评估未受累直肠粘膜的 4D-ELF 特征对于未来肿瘤的发生具有前所未有的敏感性和阳性预测价值 (>98%)。 人体试点研究证实了这些新型生物标志物的前景。 我们建议在结肠镜检查期间使用内窥镜兼容的 4D-ELF 探头进一步验证这些光谱标记。 基于 500 名患者的直肠 4D-ELF 分析，我们将制定晚期息肉/癌症的发生和肿瘤排除的预测规则（从而确定不需要进一步筛查的亚组）。 我们将前瞻性地在 750 名患者身上测试这些规则。 此外，我们将使用遗传性非息肉病性结直肠癌和家族性腺瘤性息肉病作为范例，研究 4D-ELF 无与伦比的敏感性是否可以检测由遗传倾向引起的长期 CRC 风险。 我们将评估光谱标记识别突变和预测表型表现的能力。 将来，这些光谱标记可以在直肠检查期间使用 4D-ELF 探针进行测定，从而为确定最佳 CRC​​ 筛查方案提供实用且准确的方法。