Great Lakes/New England Clinical Validation Center

描述(由申请人提供)：请求通过U01机制继续支持早期检测研究网络(EDRN)的新英格兰大湖区(GLNE)临床验证中心(CVC)。GLNE CVC是一个高度合作的多机构联盟，旨在开发、实施和分析用于验证结直肠腺癌和其他G1恶性肿瘤早期检测的生物标志物的试验。在过去的5年里，GLNE开发了一个高质量的生物样本库，收集了来自结直肠和下段食道肿瘤患者和对照的样本。GLNE具有16个用于早期发现结直肠癌的生物标志物和3个用于检测下食管化生向不典型增生和癌进展的生物标志物的初步特征。GLNE与5个生物标记物开发实验室、4个生物标记物参考实验室、EDRN DMCC和5个产业合作伙伴合作，出版了23篇稿件，其中包括与其他EDRN中心合作的15篇稿件。在下一批赠款期间，GLNE-CVC建议：1.以结肠镜检查为金标准，确定Vimentin甲基化、Galectin-3配体、确切的粪便DNA小组和粪便免疫化学试验(FIT)在早期检测结直肠肿瘤方面的表现；2.确定Vimentin甲基化、Galectin-3配体、Exact Science粪便DNA小组或任何未来单独的生物标志物在检测结直肠癌和高度不典型增生方面是否优于粪便免疫化学试验；3.确定粪便、Galectin-3配体、精密科学粪便DNA板或任何未来的单个生物标志物或将其组合在一起检测结直肠癌和高度不典型增生的波形蛋白甲基化的筛查性能；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研究人员用于未来的验证和生物标志物的发现研究。这些目标将通过一个由大学和社区Gl诊所组成的多机构联盟来解决，该联盟招募的人类受试者在符合探头的协议下接受结肠镜检查。该协议要求实施详细的生物样本收集和管理标准操作程序，并将这些生物样本与符合EDRN标准的数据元素相关联。数据将由EDRN数据管理和协调中心进行管理和分析。将为未来的生物标记物结直肠癌早期检测验证试验收集生物样本，并支持EDRN生物标记物的发现和预验证。

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.