Aptamers as Proteomic Tools for Pancreatic Cancer Biomarker Identification

适体作为胰腺癌生物标志物鉴定的蛋白质组学工具

• 批准号: 8950503
• 负责人: Rebekah White
• 金额: $ 20.75万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8950503
• 关键词: Affinity; Affinity Chromatography; Anorexia; Antibodies; Benign; Binding; Biological; Biological Assay; Biological Markers; Blood; Blood specimen; Body Fluids; Body Weight decreased; CA-19-9 Antigen; Cancer Etiology; Cancer Patient; Cancer cell line; Cancerous; Carcinoembryonic Antigen; Cell Line; Cells; Cessation of life; Country; DNA; Detection; Development; Diabetes Mellitus; Diagnosis; Diagnostic tests; Disease; Ductal Epithelial Cell; Dyspepsia; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Excision; Family history of; Future; Goals; Human; In Vitro; Interferometry; Label; Lead; Libraries; Ligands; Malignant Neoplasms; Malignant neoplasm of pancreas; Mass Spectrum Analysis; Methods; Oligonucleotides; Operative Surgical Procedures; Optics; Pancreas; Pancreatic Diseases; Patients; Post-Translational Protein Processing; Prospective Studies; Proteins; Proteomics; RNA; Reagent; Relative (related person); Resected; Resistance; Risk; Sampling; Serum; Serum Proteins; Specificity; Staging; Surface Plasmon Resonance; Symptoms; Techniques; Testing; aptamer; base; chronic pancreatitis; combinatorial; cyclophilin B; healthy volunteer; high risk; novel; nuclease; pancreatic cancer cells; prospective; protein complex; protein folding; public health relevance; screening; tool; tumor; validation studies

 DESCRIPTION (provided by applicant): The symptoms of pancreatic cancer are usually non-specific and late. Existing blood tumor biomarkers, such as carbohydrate antigen 19-9 (CA19-9), are not sensitive and specific enough to serve as useful screening tests. Tools for earlier detection could increase the proportion of patients who are diagnosed at early stages and potentially cured with surgical resection. Aptamers are oligonucleotide (RNA or DNA) molecules that directly bind to proteins with high specificity and can be used for the dual purpose of identifying novel biomarkers and detecting them in body fluids. We used a novel selection method (known as secretome selection) to identify aptamers that bind to proteins that are secreted by cultured pancreatic cancer cells but not to those secreted by non-cancerous pancreatic cells. One winning aptamer from this selection binds Cyclophilin B (CypB), a protein that has not previously been investigated as a blood biomarker for pancreatic cancer. We have demonstrated that CypB serum levels discriminate well between pancreatic cancer patients and healthy volunteers but not as well between patients with pancreatic cancer and patients with benign pancreatic disease. Our primary hypothesis is that a similar positive/negative aptamer selection strategy can be applied to serum samples from patients with pancreatic cancer and benign pancreatic disease to identify novel serum biomarkers that are specific for pancreatic cancer. The specific aims of this project are: 1) To identify additional pancreatic cancer biomarkers using an aptamer selection strategy applied to blood samples from human patients. 2) To develop assays based on these selected aptamers (including the CypB aptamer) that could be used clinically for the detection of blood biomarkers. 3) To retrospectively evaluate whether these candidate biomarkers can distinguish between patients with early pancreatic cancer, patients with benign pancreatic diseases, and unaffected patients. The successful completion of this project will lead to the identification of new biomarkers that may be useful for the diagnosis, staging, and/or treatment of pancreatic cancer. Moreover, this approach to biomarker selection can be generalized to other cancers for which better biomarkers are needed.

 描述（由申请人提供）：胰腺癌的症状通常是非特异性的并且是晚期的，现有的血液肿瘤生物标志物，例如碳水化合物抗原 19-9 (CA19-9)，不够灵敏和特异性，不足以用作有用的筛查测试。早期检测工具可以增加早期诊断并可能通过手术切除治愈的患者比例。适体是寡核苷酸（RNA 或 DNA）分子，可直接与蛋白质结合，具有高特异性，可用于识别新的生物标志物并在体液中检测它们的双重目的我们使用了一种新的选择方法（称为分泌组选择）来识别与培养的胰腺癌细胞分泌的蛋白质结合但不与非癌性细胞分泌的蛋白质结合的适体。该选择中的一个获胜适体与亲环蛋白 B (CypB) 结合，这是一种以前未曾被研究为胰腺癌血液生物标志物的蛋白质。水平在胰腺癌患者和健康志愿者之间可以很好地区分，但在胰腺癌患者和良性胰腺疾病患者之间则不然。我们的主要假设是，类似的阳性/阴性适体选择策略可以应用于胰腺癌患者的血清样本。和良性胰腺疾病，以确定胰腺癌特异性的新型血清生物标志物。该项目的具体目标是：1) 使用应用于血液样本的适体选择策略来确定其他胰腺癌生物标志物。 2) 开发基于这些选定的适体（包括 CypB 适体）的检测方法，可用于临床检测血液生物标志物。 3) 回顾性评估这些候选生物标志物是否可以区分早期胰腺癌患者，该项目的成功完成将有助于鉴定出可能对良性胰腺疾病患者和未受影响的患者有用的新生物标志物。 此外，这种生物标志物选择方法可以推广到需要更好生物标志物的其他癌症。