Biomarker Reference Laboratory, EDRN

描述（由申请人提供）：本申请的目标是在阿拉巴马大学伯明翰分校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，修改和排除潜在的早期检测方法。发展的组成部分将包括将方法学转换为高通量方法、分析局限性和制定标准操作程序。由于研究人员的核心小组来自UAB病理学系的肿瘤转化研究项目，所有这些研究人员都致力于并具有生物标志物分析的专业知识。该小组包括病理学家和基础研究人员，他们在皮肤、头颈部、肺部、结肠直肠、胰腺、乳房、卵巢和子宫颈的肿瘤过程方面具有专业知识，并在以下方面拥有技术专长和资源：表面增强激光解吸/电离飞行时间质谱（SELDI-TOF-MS）、多维凝胶分析蛋白质纯化、高通量ELISA、多重免疫测定、组织基质阵列（斑点和组织柱）的构建、计算机细胞形态分析、免疫组织化学（亮场荧光、共聚焦显微镜）、原位杂交、单次和多次实时定量PCR、其他PCR技术、免疫磁分离、组织资源和验证研究的实验设计。一个关键资源是分析患者特征（年龄、性别、种族、营养状况等）对疾病进展影响的专业知识。通过UAB综合癌症中心和人类遗传学中心以及四个UAB孢子，核心研究人员的专业知识得到了资源的补充。此外，还介绍了一个校外学术和商业顾问和资源网络。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证明。UAB- brl在EDRN中作为关键资源的能力已被UAB在当前EDRN中成功地作为生物标志物验证实验室的事实所证明。在这个角色中，UAB参与了使用尿液沉积物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识别血清中预测前列腺腺癌存在的蛋白质特征的验证研究的主要验证实验室。提出了一个发展项目，其中将确定固定剂和抗原检索技术对实时定量PCR的影响；对固定活检标本和档案材料进行这种分析的能力将大大促进早期发现标记物的发展。

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.