Analysis of serum folate receptor and antibody level for ovarian cancer detection

卵巢癌检测血清叶酸受体及抗体水平分析

• 批准号: 7288266
• 负责人: Keith L. Knutson
• 金额: $ 7.19万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-19 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7288266
• 关键词: Antibodies; Applications Grants; Archives; Autoantibodies; Binding; Biological Assay; Biological Markers; Blood Circulation; Brain; Breast; Cancer Patient; Case-Control Studies; Clinic; Data; Defect; Detection; Development; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Disease; Early Detection Research Network; Early Diagnosis; Early Intervention; Endometrium; Epithelial; Folate; Funding; Future; Goals; Human; Individual; Invasive; Kidney; Knowledge; Malignant Neoplasms; Malignant neoplasm of ovary; Measures; Membrane; Metabolic; Methodology; Methods; Mucinous; Normal Cell; Numbers; Ovarian; Ovarian Carcinoma; Ovarian Surface Epithelial-Stromal Tumor; Ovary; Patients; Play; Predictive Value; Prevention; Probability; Proteins; Range; Regulation; Risk Factors; Role; Sample Size; Screening for Ovarian Cancer; Screening for cancer; Serum; Serum Markers; Serum Proteins; Staging; Test Result; Testing; Therapeutic; Tumor Markers; United States National Institutes of Health; Woman; Work; base; design; folate-binding protein; human FOLR1 protein; human disease; improved; prognostic; tumor; tumor progression

DESCRIPTION (provided by applicant): Currently, only a limited number of serum protein markers exist for a range of tumors, and most have not proved useful for early detection. Membrane-bound folate receptor (FR) alpha is a promising tumor marker for detection of FR alpha-positive tumors. Studies of human tumors show that, FR alpha is over-expressed in epithelial tumors of the ovary, kidney, endometrium, breast and brain compared to normal cells, is identifiable in early disease, increases with tumor progression and stage, and is associated with decreased survival. Importantly, FR alpha is released as a soluble form (sFR alpha) into the circulation and is relatively absent in normal serum, suggesting it may be a promising serum marker for FR alpha-positive tumors. In addition, FR alpha autoantibodies are detected in serum of individuals with folate-related disorders, signifying that the autoantibodies could be another potential biomarker of FR alpha-positive tumors. To our knowledge, no study has investigated their presence in the serum of individuals with FR alpha-positive tumors. We hypothesize that sFR alpha and FR alpha antibodies will be higher among women with ovarian cancer than women without cancer and, specifically, higher among women with early-stage cancer. We focus on ovarian cancer in this application because FR alpha is over-expressed in >90% of non-mucinous epithelial ovarian tumors and is expressed at much lower levels in other tumors; therefore, we anticipate greater likelihood of designing and optimizing assays for FR alpha detection using serum from these patients; and because ovarian cancer is one of the most difficult human diseases to diagnose and treat. Our approach will be to design, develop, and optimize quantitative assays to measure these analytes, and apply each assay to archived, pre-therapeutically collected serum from 30 patients with ovarian cancer (15 early- stage) and 30 women without cancer who participated in a case-control study at Mayo Clinic. Our intent at this initial stage of biomarker discovery is to assess if our assays can detect the analytes truthfully by validating them against FR alpha expression levels in the tumors of the cases and from serum of controls without cancer as reference groups. The data generated from this study, if positive as we expect, will be the basis of a larger analysis that apply these assays to other tumor types with several aims including assessment of diagnostic potential, which is the ultimate goal of biomarker discovery.

描述（由申请人提供）： 目前，只有有限数量的血清蛋白标记物存在于一系列肿瘤中，并且大多数尚未被证明对早期检测有用。膜结合叶酸受体（FR）α是一种有前途的肿瘤标志物，用于检测FR α阳性肿瘤。人类肿瘤的研究表明，与正常细胞相比，FR α在卵巢、肾脏、子宫内膜、乳腺和脑的上皮肿瘤中过表达，在早期疾病中可识别，随着肿瘤进展和分期而增加，并且与生存期降低相关。重要的是，FR α以可溶形式（sFR α）释放到循环中，在正常血清中相对不存在，这表明它可能是FR α阳性肿瘤的有希望的血清标志物。此外，在叶酸相关疾病个体的血清中检测到FR α自身抗体，这意味着自身抗体可能是FR α阳性肿瘤的另一种潜在生物标志物。据我们所知，还没有研究调查它们在FR α阳性肿瘤个体血清中的存在。我们假设，sFR α和FR α抗体在卵巢癌患者中高于未患癌症的女性，特别是在早期癌症患者中更高。我们在本申请中关注卵巢癌，因为FR α在>90%的非粘液性上皮性卵巢肿瘤中过表达，并且在其他肿瘤中以低得多的水平表达;因此，我们预期更有可能设计和优化使用来自这些患者的血清的FR α检测的测定;因为卵巢癌是最难诊断和治疗的人类疾病之一。我们的方法将是设计，开发和优化定量分析来测量这些分析物，并将每种测定应用于存档的、治疗前收集的血清，这些血清来自30名卵巢癌患者（15名早期）和30名未患癌症的妇女，这些妇女参加了马约诊所的病例对照研究。在生物标志物发现的初始阶段，我们的目的是评估我们的检测方法是否可以通过验证病例肿瘤中的FR α表达水平和作为参考组的无癌症对照血清中的FR α表达水平来真实地检测分析物。本研究产生的数据，如果如我们预期的那样是阳性的，将成为更大规模分析的基础，该分析将这些检测方法应用于其他肿瘤类型，其目的包括评估诊断潜力，这是生物标志物发现的最终目标。