Great Lakes/New England Clinical Validation Center

描述（由申请方提供）：请求通过U 01机制继续支持早期检测研究网络（EDRN）的五大湖新英格兰（GLNE）临床验证中心（CVC）。GLNE CVC是一个高度协作的多机构联盟，旨在开发、实施和分析用于验证用于早期检测结直肠腺癌和其他GI恶性肿瘤的生物标志物的试验。在过去的5年中，GLNE已经开发了一个高质量的生物样本库，其中包含从结直肠和下食管肿瘤受试者和对照受试者中采集的样本。GLNE初步表征了16种用于早期检测结直肠腺癌的生物标志物和3种用于检测食管下段化生进展为异型增生和癌的生物标志物。GLNE与5个生物标志物开发实验室，4个生物标志物参考实验室，EDRN DMCC和5个工业合作伙伴合作，出版了23篇手稿，其中15篇手稿与其他EDRN中心合作。在下一个授权时段中，GLNE-CVC建议1.确定波形蛋白甲基化、半乳糖凝集素-3配体、精确粪便DNA板和粪便免疫化学试验（FIT）的性能，以结肠镜检查作为金标准用于早期检测结直肠肿瘤; 2.确定波形蛋白甲基化、半乳糖凝集素-3配体、Exact sciences粪便DNA组或任何未来单独的个体生物标志物是否比粪便免疫化学测试在检测结直肠腺癌和高度异型增生方面表现更好; 3.确定粪便中波形蛋白甲基化、半乳糖凝集素-3配体、Exact sciences粪便DNA组或任何未来的个体生物标志物或FIT一起用于检测结直肠腺癌和高度异型增生的筛选性能;以及4.建立适当保存的粪便、血清、血浆、尿液和DNA人类生物标本的档案，供EDRN研究者用于未来的验证和生物标志物发现研究。这些目标将由大学和社区GI实践的多机构联盟来解决，该联盟招募根据PRoBE兼容方案进行筛选结肠镜检查的人类受试者。该方案要求实施详细的生物样本采集和管理标准操作规程，并将这些生物样本与EDRN合规数据元素相关联。数据将由EDRN数据管理和协调中心进行管理和分析。将收集生物样品用于未来的生物标志物结直肠癌早期检测验证试验，并支持EDRN生物标志物的发现和预验证。

DESCRIPTION (provided by applicant): Continued support of the Great Lakes New England (GLNE) Clinical Validation Center (CVC) of the Early Detection Research Network (EDRN) via the U01 mechanism is requested. The GLNE CVC is a highly collaborative, multi-institutional consortium designed to develop, implement and analyze trials for the validation of biomarkers for the early detection of colorectal adenocarcinoma and other Gl malignancies. Over the last 5 years, the GLNE has developed a high quality biosample repository of samples collected from human subjects with colorectal and lower esophageal neoplasias and controls. The GLNE has preliminary characterization of 16 biomarkers for the early detection of colorectal adenocarcinoma and 3 biomarkers for the detection of progression of lower esophageal metaplasia to dysplasia and carcinoma. The GLNE has collaborated with 5 biomarker developmental laboratories, 4 biomarker reference laboratories, the EDRN DMCC, and 5 industrial partners publishing 23 manuscripts including 15 manuscripts collaborating with other EDRN centers. In the next grant period, the GLNE-CVC proposes to 1. To determine the performance of vimentin methylation, galectin-3 ligand, the Exact stool DNA panel, and fecal immunochemical test (FIT) for the early detection of colorectal neoplasia using colonoscopy as the gold standard; 2. To determine if vimentin methylation, galectin-3 ligand, Exact sciences stool DNA panel, or any future individual biomarker alone performs better than fecal immunochemical testing for the detection of colorectal adenocarcinoma and high grade dysplasia; 3. To determine the screening performance of vimentin methylation in stool, galectin-3 ligand, Exact sciences stool DNA panel, or any future individual biomarker or FIT together for detection of colorectal adenocarcinoma and high grade dysplasia; and 4. To establish an archive of appropriately preserved stool, serum, plasma, urine, and DNA human biospecimens to be used by EDRN investigators for future validation and biomarker discovery research. These aims will be addressed by a multi-institutional consortium of university and community Gl practices recruiting human subjects undergoing screening colonoscopy under a PRoBE compliant protocol. The protocol requires the implementation of detailed standard operating procedures for biosample collection and management and associates these biosamples with EDRN compliant data elements. The data will be managed and analyzed by the EDRN data management and coordinating center. Biosamples will be collected for future biomarker colorectal cancer early detection validation trials and to support EDRN biomarker discovery and prevalidation.