Spectroscopic Markers to Risk-Stratify Colonic Neoplasia

描述（由申请人提供）：为了优化结直肠癌（CRC）筛查的结肠镜检查的风险-收益和成本-效果，风险分层至关重要。利用“场效应”，即容易接近的结肠粘膜（即直肠）应反映整个结肠的肿瘤风险，是一个有吸引力的主张。然而，目前的标志物，如远端/直肠腺瘤和异常隐窝灶（ACF）缺乏敏感性和临床应用的预测价值。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，使我们能够收集到迄今为止无法获得的关于原位活上皮纳米/微结构的定量信息。使用4D-ELF，我们在组织学正常的粘膜中发现了几个光谱特征，这些特征先于所有常规的CRC生物标志物，并作为结肠癌发生实验模型中“场效应”的最早标记之一。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。初步研究证实了这些光谱标记与人类的相关性。该项目将测试直肠光谱标记物可以预测并发和未来结肠肿瘤发生的假设。在本应用中，我们建议构建一个内窥镜兼容的4D-ELF探针，以评估直肠光谱标记物（已建立的和新的）对平均风险患者结肠镜检测到的肿瘤的预测规则的性能特征。我们还将通过评估结直肠癌切除术患者的直肠ACF数和腺瘤的监测内窥镜检查来确定谱标记物预测未来肿瘤的能力。最后，我们将进行初步研究，以了解光谱标记物的生物学基础。在未来，光谱标记物可以在常规直肠检查中使用4D-ELF探针进行检测（无需肠准备或结肠镜检查），从而提供一种实用而准确的方法来确定最佳的CRC筛查方案，例如需要结肠镜检查。

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.