Spectroscopic Markers to Risk-Stratify Colonic Neoplasia

对结肠肿瘤进行风险分层的光谱标记物

• 批准号: 6969365
• 负责人: Vadim Backman
• 金额: $ 18.91万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6969365
• 关键词: adenoma; bioimaging /biomedical imaging; biomarker; cadherins; cancer risk; carcinogenesis; clinical research; colorectal neoplasms; diagnosis design /evaluation; early diagnosis; endoscopy; fiber optics; gastrointestinal imaging /visualization; guanine nucleotide binding protein; human subject; intestinal mucosa; light scattering; miniature biomedical equipment; molecular /cellular imaging; molecular pathology; neoplasm /cancer diagnosis; neoplasm /cancer genetics; preneoplastic state; rectum /anus

DESCRIPTION (provided by applicant): In order to optimize the risk-benefit and cost-effectiveness of colonoscopy for colorectal cancer (CRC) screening, risk-stratification is of paramount importance. Exploitation of the "field effect" in which readily accessible colonic mucosa (i.e. rectum) should reflect the neoplastic risk throughout the colon, is an attractive proposition. However, current markers such as distal/rectal adenomas and aberrant crypt foci (ACF) lack the sensitivity and predictive value for clinical utility. We have recently developed four-dimensional elastic light scattering "fingerprinting" (4D-ELF), a biomedical optics technology that allows us to gather heretofore unattainable quantitative information about nano/micro-architecture of living epithelia in situ. Using 4D-ELF, we discovered several spectral signatures in histologically normal mucosa that preceded all conventional biomarkers of CRC and served as one of the earliest markers of the "field effect" in experimental models of colon carcinogenesis. Indeed, rectal spectral markers had unprecedented sensitivity, specificity, positive and negative predictive values for neoplastic risk. Pilot studies confirmed the relevance of these spectral markers to humans. The proposed project will test the hypothesis that rectal spectral markers can predict the occurrence of concurrent and future colonic neoplasia. In this application, we propose to construct an endoscopically compatible 4D-ELF probe in order to assess performance characteristic of prediction rules of rectal spectral markers (established and novel) for neoplasia detected on colonoscopy in average risk patients. We will also ascertain the ability of spectral markers to predict future neoplasia by evaluating rectal ACF number and adenoma occurrence in surveillance endoscopies of patients undergoing CRC resection. Finally, we will perform initial studies to understand the biological basis of spectral markers. In the future, spectral markers may be assayed with a 4D-ELF probe during a routine rectal examination (without the need for bowel preparation or colonoscopy) thus providing a practical and accurate means of determining the optimal CRC screening regimen, such as the need for colonoscopy.

描述（由申请人提供）：为了优化结肠镜检查用于结直肠癌（CRC）筛查的风险效益和成本效益，风险分层至关重要。利用“场效应”，其中容易接近的结肠粘膜（即直肠）应该反映整个结肠的肿瘤风险，是一个有吸引力的主张。然而，目前的标记物，例如远端/直肠腺瘤和异常隐窝病灶（ACF）缺乏临床实用性的敏感性和预测价值。我们最近开发了四维弹性光散射“指纹”（4D-ELF），这是一种生物医学光学技术，使我们能够收集迄今为止无法获得的有关活体上皮细胞原位纳米/微米结构的定量信息。使用 4D-ELF，我们在组织学正常粘膜中发现了几个光谱特征，这些特征先于 CRC 的所有常规生物标志物，并作为结肠癌发生实验模型中“场效应”的最早标志物之一。事实上，直肠光谱标记物对肿瘤风险具有前所未有的敏感性、特异性、阳性和阴性预测值。试点研究证实了这些光谱标记与人类的相关性。拟议的项目将测试直肠光谱标记可以预测并发和未来结肠肿瘤发生的假设。在此应用中，我们建议构建一种内窥镜兼容的 4D-ELF 探针，以评估直肠光谱标记物（已建立的和新颖的）预测规则的性能特征，用于在普通风险患者中通过结肠镜检查检测到的肿瘤。我们还将通过评估接受 CRC 切除的患者的监测内窥镜检查中的直肠 ACF 数量和腺瘤发生情况，确定光谱标记物预测未来肿瘤形成的能力。最后，我们将进行初步研究以了解光谱标记的生物学基础。将来，可以在常规直肠检查期间使用 4D-ELF 探针检测光谱标记（无需肠道准备或结肠镜检查），从而为确定最佳 CRC​​ 筛查方案（例如是否需要结肠镜检查）提供实用且准确的方法。