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: 7196223
• 负责人: Keith L. Knutson
• 金额: $ 7.4万
• 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 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7196223
• 关键词: antibody receptor; clinical research; folate; neoplasm /cancer; ovary neoplasms; serum

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，而且大多数已被证明对早期检测没有用处。膜结合叶酸受体(FRα)是检测FRα阳性肿瘤的一种很有前途的肿瘤标志物。对人类肿瘤的研究表明，与正常细胞相比，FRα在卵巢、肾脏、子宫内膜、乳腺和大脑的上皮性肿瘤中过度表达，可在早期疾病中发现，随着肿瘤的进展和分期而增加，并与生存率下降有关。重要的是，FRα以可溶性形式(SFRα)释放到循环中，在正常血清中相对缺乏，这表明它可能是FRα阳性肿瘤的一个有前途的血清标记物。此外，在叶酸相关疾病患者的血清中检测到FRα自身抗体，这意味着该自身抗体可能是FRα阳性肿瘤的另一个潜在的生物标志物。据我们所知，还没有研究研究它们在FRα阳性肿瘤患者的血清中的存在。我们假设卵巢癌患者的SFRα和FRα抗体水平高于非癌症患者，尤其是早期癌症患者。我们在这一应用中重点关注卵巢癌，因为FRα在90%的非粘液性卵巢上皮性肿瘤中过度表达，而在其他肿瘤中的表达水平要低得多；因此，我们预计使用这些患者的血清来设计和优化FRα检测方法的可能性更大；而且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，并将每种分析应用于存档的、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名参加梅奥诊所病例对照研究的非癌症女性。在生物标记物发现的这个初始阶段，我们的意图是评估我们的检测方法是否能够通过在病例的肿瘤和非癌症对照组的血清中验证它们的FRα表达水平来真实地检测分析物。这项研究产生的数据，如果像我们预期的那样是阳性的，将成为更大规模分析的基础，该分析将这些分析应用于其他肿瘤类型，目的有几个，包括评估诊断潜力，这是发现生物标记物的最终目标。