Nanoscale/Molecular analysis of Fecal Colonocytes for Colorectal Cancer Screening

用于结直肠癌筛查的粪便结肠细胞的纳米级/分子分析

• 批准号: 8529475
• 负责人: Vadim Backman
• 金额: $ 53.88万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8529475
• 关键词: Age; Algorithms; American; Animals; Architecture; Biological; Biophotonics; Cancer Etiology; Cells; Cervical Cancer Screening; Cessation of life; Characteristics; Clinical; Colon; Colon Carcinoma; Colonoscopy; Colorectal Cancer; Colposcopy; Contrast Media; Data; Data Analyses; Demographic Aging; Detection; Development; Disease; Distal; Dysplasia; Endoscopy; Ensure; Epigenetic Process; Epithelial Cells; Epithelium; Feces; Fingerprint; Funding; Future; Gender; General Population; Genetic; Goals; Guidelines; Hemorrhage; Histologic; Image; Individual; Lead; Lesion; Life; Location; Lung; Malignant Neoplasms; Measures; Medicine; Methods; MicroRNAs; Microsatellite Instability; Microscopy; Modeling; Molecular; Molecular Analysis; Mucous Membrane; Mucous body substance; Neoplasms; Optics; Pancreas; Pap smear; Pathway interactions; Patients; Performance; Polypectomy; Population; Populations at Risk; Procedures; Protocols documentation; Refractive Indices; Risk; Solutions; Specimen Handling; Stratification; Techniques; Technology; Testing; Tobacco; Translating; Ursidae Family; Validation; Variant; Villous; adenoma; base; cancer risk; carcinogenesis; clinical application; colon carcinogenesis; colorectal cancer screening; cost; cost effective; improved; innovation; instrument; minimally invasive; molecular marker; nanoscale; neoplastic; neoplastic cell; non-compliance; novel; patient population; pre-clinical; public health relevance; rectal; screening; statistics; technology development; tool

DESCRIPTION (provided by applicant): Existing guidelines recommend colorectal cancer (CRC) screening for all patients over age 50. However, CRC remains the second leading cause of cancer death among Americans largely because colonoscopic screening of all the >100 million Americans over age 50 is unfeasible for both patient-related (non-compliance) and societal (inadequate endoscopic capacity and funding) reasons. Furthermore, the current practice of colonoscopy on the 3average risk4 population is remarkably inefficient2only ~6% of the screening population has significant neoplasia (advanced adenomas). Thus, a simple, non-invasive risk-stratification technique is critical to better target patients for colonoscopy. Stool analysis would be an ideal test that would engender the best patients6 compliance, although current stool tests assessing tumor cells or blood loss have dismal sensitivity. We propose a novel, more robust approach that utilizes mucus layer fecal colonocytes which are abraded from the epithelium and thus represent field carcinogenesis (the genetic/environmental fingerprint of neoplastic risk). Based on our preliminary data (156 patients), we hypothesize that the analysis of two complementary facets, nanostructural and molecular (microRNA) alterations, in mucus layer fecal colonocytes will serve as a highly accurate means of identifying field carcinogenesis and thereby serve as a non-invasive CRC screening test. Our approach is based on the combination of a novel biophotonics technology, partial wave spectroscopic microscopy (PWS), that is uniquely capable of imaging and quantification of the statistics of cell nanoscale organization and a new method to get high quality non-apoptotic fecal colonocytes in a practical fashion. In preclinical and clinical models, the performance characteristics of PWS and microRNA were outstanding, thus providing promise for a screening test. There are several requisite steps prior to the future definitive clinical validation. We will develop high-throughput PWS technology and identify the cellular location of the nanoarchitectural alterations. We will formulate and prospectively test a prediction rule that combines both nanostructural and molecular alterations. This project will confirm that nanostructural/ molecular stool analysis may provide sensitive, non-invasive risk-stratification tool, thereby heralding the era of personalized medicine for CRC population screening.

描述(由申请人提供)：现有指南建议对所有50岁以上的患者进行结直肠癌(CRC)筛查。然而，结直肠癌仍然是美国人癌症死亡的第二大原因，很大程度上是因为对50岁以上的1亿美国人进行结肠镜筛查是不可行的，这既是患者相关的(不符合规定的)原因，也是社会(内窥镜检查能力和资金不足)的原因。此外，目前结肠镜检查对3个平均风险人群的效率非常低。2只有~6%的筛查人群有明显的肿瘤形成(晚期腺瘤)。因此，一种简单的、非侵入性的风险分层技术对于更好地针对患者进行结肠镜检查至关重要。粪便分析将是一种理想的检测方法，它将产生最好的患者依从性，尽管目前评估肿瘤细胞或失血的粪便检测具有令人沮丧的敏感性。我们提出了一种新的、更健壮的方法，它利用粘液层粪便结肠细胞，这些细胞从上皮中磨损，从而代表现场癌变(肿瘤风险的遗传/环境指纹)。基于我们的初步数据(156名患者)，我们假设对粘液层粪便结肠细胞中纳米结构和分子(MicroRNA)变化这两个互补方面的分析将作为一种高度准确的手段来识别现场癌变，从而作为一种非侵入性的CRC筛查测试。我们的方法是基于一种新的生物光子学技术--部分波光谱显微镜(PWS)，它独特地能够成像和量化细胞纳米级组织的统计数据，以及一种实用的高质量非凋亡性粪便结肠腺细胞的新方法。在临床前和临床模型中，PWS和microRNA的性能特征突出，因此为筛查测试提供了希望。在未来的最终临床验证之前，有几个必要的步骤。我们将开发高通量PWS技术，并确定纳米结构变化的蜂窝位置。我们将制定并前瞻性地测试一种结合了纳米结构和分子变化的预测规则。该项目将证实，纳米结构/分子粪便分析可能提供敏感的、非侵入性的风险分层工具，从而预示着用于结直肠癌人群筛查的个性化药物时代的到来。