Biomarkers with Biological Function in Ovarian Carcinoma

描述（由申请人提供）：通过基因阵列分析，已鉴定出10个编码细胞粘附分子的基因，这些基因在卵巢癌组织样本中上调，并且对卵巢癌具有相对特异性。该项目的目的是鉴定一个或多个细胞粘附分子，其中：(a)改变的基因表达与改变的蛋白质表达相对应，(b)蛋白质表达与患者信息相关，(c)分子的生物学相关性可以定义为卵巢癌。这些分子可能作为早期检测的生物标志物或卵巢癌复发的检测。此外，这些分子可能被证明在卵巢癌的新治疗方案的设计有用。在Aim #1中，将通过免疫组织化学在卵巢癌组织样本中定位十种细胞粘附蛋白与其他组织类型。它们在组织样品中的分子量将通过免疫印迹或放射免疫沉淀来验证。在目标#2中，卵巢癌患者的血液和腹水样本将通过免疫印迹法或放射免疫沉淀法筛选蛋白质的存在。通过ELISA或放射免疫分析法测定患者循环中每种蛋白质的水平。统计分析将用于确定组织分布、蛋白质表达、蛋白质循环水平、组织组织学和患者预后/信息之间的关系。在Aim #3中，将对新鲜卵巢癌患者样本和已建立细胞系的表面和废培养基中的蛋白质表达水平进行定量。这些细胞粘附蛋白在卵巢癌细胞粘附、侵袭和聚集形成中的作用将通过阻断单克隆抗体和RNA干扰来阐明。细胞粘附蛋白的表达/分泌水平与生物功能活性和患者信息之间的关系将被确定。

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.