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，针对一系列肿瘤仅存在有限数量的血清蛋白标记物，并且大多数尚未被证明可用于早期检测。膜结合叶酸受体 (FR) α 是一种很有前景的肿瘤标志物，可用于检测 FR α 阳性肿瘤。对人类肿瘤的研究表明，与正常细胞相比，FR α 在卵巢、肾、子宫内膜、乳腺和脑的上皮肿瘤中过度表达，在疾病早期即可识别，随着肿瘤进展和阶段的增加而增加，并且与生存。重要的是，FR α 以可溶形式 (sFR α) 释放到循环中，并且在正常血清中相对不存在，这表明它可能是 FR α 阳性肿瘤的有前途的血清标志物。此外，在患有叶酸相关疾病的个体的血清中检测到 FR α 自身抗体，这表明自身抗体可能是 FR α 阳性肿瘤的另一个潜在生物标志物。据我们所知，尚无研究调查它们在 FR α 阳性肿瘤个体血清中的存在。我们假设患有卵巢癌的女性中的 sFR α 和 FR α 抗体会比未患癌症的女性更高，特别是在患有早期癌症的女性中更高。我们在此应用中重点关注卵巢癌，因为 FR α 在 >90% 的非粘液性上皮性卵巢肿瘤中过度表达，而在其他肿瘤中表达水平低得多；因此，我们预计使用这些患者的血清设计和优化 FR α 检测方法的可能性更大；因为卵巢癌是人类最难诊断和治疗的疾病之一。我们的方法是设计、开发和优化定量测定来测量这些分析物，并将每种测定应用于从 30 名卵巢癌患者（15 名早期）和 30 名未患癌症的女性（参与研究）中存档的、治疗前收集的血清。梅奥诊所的一项病例对照研究。我们在生物标志物发现的初始阶段的目的是通过对照病例肿瘤中的 FR α 表达水平以及作为参考组的无癌症对照血清中的 FR α 表达水平来验证分析物，从而评估我们的测定是否能够真实地检测到分析物。这项研究产生的数据，如果如我们预期的那样，将成为更大规模分析的基础，将这些检测方法应用于其他肿瘤类型，其几个目的包括评估诊断潜力，这是生物标志物发现的最终目标。