Biomarkers with Biological Function in Ovarian Carcinoma

描述(申请人提供)：通过基因阵列分析，已经确定了10个编码细胞黏附分子的基因，这些基因在卵巢癌组织样本中上调，并且是卵巢癌相对特异的。本项目的目标是确定一个或多个细胞黏附分子，其中：(A)基因表达改变对应于蛋白质表达改变，(B)蛋白质表达与患者信息相关，以及(C)分子的生物学相关性可与卵巢癌相关。这些分子有可能作为卵巢癌的早期检测或复发检测的生物标志物。此外，这些分子可能会被证明对设计卵巢癌的新治疗方案很有用。在目标1中，10个细胞黏附蛋白将通过免疫组织化学定位于卵巢癌和其他组织类型的组织样本中。它们在组织样本中的相对分子质量将通过免疫印迹或放射免疫沉淀来验证。在AIM#2中，将通过免疫印迹或放射免疫沉淀对卵巢癌患者的血液和腹水样本进行蛋白质筛选。患者循环中每种蛋白质的水平将通过ELISA法或放射免疫法进行定量。统计分析将被用来确定组织分布、蛋白质表达和循环蛋白质水平与组织组织学和患者结局/信息之间的联系。在目标#3中，将对新鲜卵巢癌患者样本和已建立的细胞系的表面和废液中蛋白质的表达水平进行定量。这些细胞黏附蛋白在卵巢癌细胞黏附、侵袭和聚集形成中的作用将通过阻断单抗和RNA干扰来阐明。将确定细胞黏附蛋白的表达/分泌水平与生物学功能活动和患者信息之间的联系。

DESCRIPTION (provided by applicant): Ten genes that code for cell adhesion molecules have been identified by gene array analysis that are up-regulated in ovarian carcinoma tissue samples and are relatively specific to ovarian carcinoma. The objective of this project is to identify one or more cell adhesion molecule in which: (a) altered gene expression corresponds to altered protein expression, (b) protein expression is associated with patient information, and (c) the biological relevance of the molecules can be defined with respect to ovarian carcinoma. These molecules may potentially serve as early detection biomarkers or for detection of recurrence of ovarian carcinoma. In addition, these molecules may prove useful in the design of novel therapeutic regimens for ovarian carcinoma. In Aim #1, the ten cell adhesion proteins will be localized by immunohistochemistry in tissue samples of ovarian carcinoma vs. other tissue types. Their molecular weight in tissue samples will be verified by Western immunoblotting or radioimmunoprecipitation. In Aim #2, blood and ascites samples from patients with ovarian carcinoma will be screened for the presence of the proteins by Western immunoblotting or radioimmunoprecipitation. The level of each protein in the patients' circulation will be quantitated by ELISA or radioimmunoassay. Statistical analysis will be used to identify the association between tissue distribution, protein expression, and circulating levels of the proteins, and tissue histology and patient outcome/information. In Aim #3, the levels of expression of the proteins on the surface and in the spent media of fresh ovarian carcinoma patient samples and established cell lines will be quantitated. The role of these cell adhesion proteins in ovarian carcinoma cell adhesion, invasion, and aggregate formation will be elucidated by use of blocking monoclonal antibodies and RNA interference. The association between levels of expression/secretion of the cell adhesion proteins with biological functional activities and patient information will be determined.