Biomarker Reference Laboratory, EDRN

描述（由申请人提供）：本申请的目标是在伯明翰的亚拉巴马大学建立一个生物标志物参考实验室（BRL），该实验室将在EDRN内发挥作用，在进入验证研究之前开发、修改和排除早期检测的潜在方法。开发的组成部分将包括将方法转换为高通量方法，分析局限性，以及制定标准操作程序。由于核心研究人员来自UAB病理学系肿瘤转化研究项目，所有这些研究人员都致力于生物标志物分析，并具有生物标志物分析方面的专业知识。该小组包括皮肤、头颈、肺、结肠直肠、胰腺、乳腺、卵巢和子宫颈肿瘤过程方面的病理学家和基础研究人员，以及表面增强激光解吸/电离飞行时间质谱方面的技术专长和资源。（SELDI-TOF-MS），多维凝胶分析蛋白纯化，高通量ELISA，多重免疫测定，组织基质阵列的构建（斑点和组织圆柱体），计算机化细胞形态计量分析，免疫组织化学（明场荧光，共聚焦显微镜），原位杂交，单次和多重真实的时间定量PCR，其它PCR技术，免疫磁性分离，组织资源，和验证研究的实验设计。一个关键的资源是分析患者特征（年龄，性别，种族，营养状况等）影响的专业知识。对疾病进展的影响核心研究人员的专业知识得到了UAB综合癌症中心和人类遗传学中心以及四个UAB孢子可用资源的补充。还描述了一个学术和商业校外顾问和资源网络。研究人员的协作能力和作为资源的能力在他们的出版物中得到了证明。UAB在当前EDRN中成功地作为生物标志物验证实验室，这一事实证明了UAB-BRL作为EDRN中关键资源的能力。在这一角色中，UAB致力于使用尿沉渣微卫星分析早期检测膀胱移行细胞癌的验证研究的设计和方案开发，并作为使用SELDI-TOF-MS的验证研究的主要验证实验室，以确定血清中预测前列腺癌存在的蛋白质特征。提出了一个发展项目，其中固定剂和抗原修复技术对真实的时间定量PCR的影响将被确定;固定活检标本和档案材料进行这种分析的能力将大大提高早期检测标记的发展。

DESCRIPTION (provided by applicant): The goal of this application is to establish a Biomarker Reference Laboratory (BRL) at the University of Alabama at Birmingham that will function within the EDRN to develop, modify and trouble-shoot potential methods of early detection prior to their entry into validation studies. Components of development will include conversion of methodologies to high-throughput methods, analysis of limitations, and development of standard-operating-procedures. As the core group of investigators has been drawn from the Program in Translational Research in Neoplasia in the Department of Pathology at UAB, all of these investigators are committed to, and have expertise in, the analysis of biomarkers. The group includes pathologists and basic researchers with expertise in neoplastic processes of the skin, head and neck, lung, colorectum, pancreas, breast, ovary and cervix, as well as technical expertise in, and resources for, surface- enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS), multidimensional gel analysis protein purification, high-throughput ELISA, multiplex immunoassays, construction of tissue matrix arrays (spotted and tissue cylinders), computerized cytomorphometric analysis, immunohistochemistry (bright field fluorescent, confocal microscopy), in situ hybridization, single and multiplex real time quantitative PCR, other PCR techniques, immunomagnetic separations, tissue resources, and experimental design of validation studies. A key resource is expertise in analysis of the effects of patient characteristics (age, sex, race nutritional status, etc.) on disease progression. The expertise of the core investigators is complemented by the resources available though the UAB Comprehensive Cancer Center and the Center for Human Genetics as well as the four UAB SPORES. A network of extramural consultants and resources, both academic and commercial, also is described. The ability of the investigators to work collaboratively and as a resource is demonstrated in their publications. The ability of the UAB-BRL to act as a key resource within the EDRN is demonstrated by the fact that UAB has functioned successfully as a Biomarker Validation Laboratory in the current EDRN. In this role, UAB worked in the design and protocol development of the validation study of using microsatellite analysis of urine sediment in the early detection of transitional cell carcinoma of the bladder and as the primary validation laboratory of the Validation Study of the use of SELDI-TOF-MS to identify protein signatures in serum that predict the presence of adenocarcinoma of the prostate. A developmental project is proposed in which the effects of fixatives and antigen retrieval techniques on real time quantitative PCR will be determined; the ability to perform such analyses on fixed biopsy specimens and archival material would greatly enhance the development of markers of early detection.