Validation Study of Select Biomarkers for the Diagnostic of Pancreatic Cancer

用于诊断胰腺癌的精选生物标志物的验证研究

• 批准号: 8237026
• 负责人: MICHELLE Ann ANDERSON
• 金额: $ 18.04万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8237026
• 关键词: American Cancer Society; Basic Science; Benign; Bile fluid; Biological Markers; Cancer Etiology; Cancerous; Carcinogenesis Mechanism; Cathepsin E; Cessation of life; Clinical; Clinical Data; Clinical Research; Colon Carcinoma; Colonic Adenoma; Cytology; Cytotoxic Chemotherapy; Cytotoxic agent; Data; Detection; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Disease; Early Diagnosis; Early treatment; Elderly; Excision; Fine needle aspiration biopsy; Future; Glycoproteins; Goals; Grant; Incidence; Individual; Inherited; Intervention; Invaded; Laboratories; Lead; Lesion; Liquid substance; Malignant Neoplasms; Malignant neoplasm of pancreas; Medical; Mentors; Molecular; Neoplasm Metastasis; Neoplastic Cell Transformation; Operative Surgical Procedures; Pancreas; Pancreatic Adenocarcinoma; Pancreatic Intraepithelial Neoplasia; Patients; Pattern; Plasma; Polymerase Chain Reaction; Population; Premalignant; Radiation; Radiation therapy; Recruitment Activity; Research; Research Personnel; Resected; Risk; Risk Assessment; S100P gene; Scientist; Screening procedure; Sensitivity and Specificity; Serum; Smoking; Specimen; Staging; Structure; Survival Rate; Techniques; Technology; Testing; Time; Tissues; Training; Ultrasonography; United States; Validation; Virulent; Woman; Work; arm; base; biobank; career; chronic pancreatitis; cohort; density; design; experience; high risk; improved; lymph nodes; mRNA Expression; maspin; men; minimally invasive; mortality; neoplastic; novel; pancreatic juice; pancreatic neoplasm; tool; tumor; validation studies

DESCRIPTION (provided by applicant): Pancreatic cancer is a highly aggressive disease representing the fourth leading cause of cancer-related deaths in the United States. Endoscopic ultrasound (EUS) technology provides a novel, minimally invasive tool to study biomarkers. The proposed project forms the scientific focus of my training grant that capitalizes on my clinical experience in EUS to determine whether a select panel of biomarkers can detect pancreatic neoplasia at an early stage. I propose a validation study of a panel of biomarkers (maspin, cathepsin E, ATDC, CEACAM-1, S100P and CEA-6) for the diagnosis of pancreatic cancer. Preliminary work using, microdissected and surgically obtained specimens has demonstrated that this panel of highly selected biomarkers is expressed and detectable using real-time PCR and successfully differentiates pancreatic cancer from normal pancreas and from chronic pancreatitis, a disease which commonly mimics pancreatic cancer clinically and confounds accurate diagnosis. This proposal will employ a surgical cohort and an endoscopic cohort. In the surgical cohort, I will determine mRNA expression of these biomarkers in tumors as well as in surrounding "normal" pancreas and precancerous lesions (pancreatic intraepithelial neoplasias), using systematic, precisely defined fine needle aspiration (FNA) specimens taken throughout the pancreas in patients undergoing surgical resection for known or suspected pancreatic cancer. In the endoscopic arm, I will determine if this panel of biomarkers alone or in combination is more sensitive or specific for diagnosis than cytology alone and if levels of expression vary based on stage and surgical resectability. Serum, plasma, pancreatic juice and bile will be collected and stored to form a biorepository in anticipation of future validation of serum or pancreatic fluid based biomarkers of pancreatic neoplasia. My career goal is to become an independent translational investigator focused on pancreatic cancer biomarkers. This training grant is proposed to release my time to enable training in molecular diagnostic technologies and experience in the design and conduct of validation trials under the guidance of accomplished mentors. I will attend courses in biomarker development and validation and in the creation of biorepositories. I will recruit patients and personally collect and analyze the specimens obtained. Completing this proposal will allow me to achieve my career goals of becoming an independent translational scientist applying carcinogenesis mechanisms and biomarker discovery technologies in the early diagnosis and risk assessment of pancreatic cancer. Such research would be expected to reduce the mortality associated with this disease.

描述（由申请人提供）：胰腺癌是一种高度侵袭性疾病，是美国癌症相关死亡的第四大原因。内镜超声（EUS）技术为研究生物标志物提供了一种新颖的微创工具。拟议的项目是我培训经费的科学重点，利用我在EUS的临床经验来确定一组选定的生物标志物是否可以在早期发现胰腺肿瘤。我建议对一组生物标志物（maspin, cathepsin E， ATDC, CEACAM-1， S100P和CEA-6）进行胰腺癌诊断的验证研究。使用显微解剖和手术获得的标本进行的初步工作表明，这组高度选择的生物标志物可以通过实时PCR表达和检测，并成功地将胰腺癌与正常胰腺和慢性胰腺炎区分开来，慢性胰腺炎通常在临床上与胰腺癌相似，但难以准确诊断。本研究将采用手术队列和内窥镜队列。在手术队列中，我将使用系统的、精确定义的细针穿刺（FNA）标本，在接受已知或疑似胰腺癌手术切除的患者的整个胰腺中，测定肿瘤以及周围“正常”胰腺和癌前病变（胰腺上皮内瘤变）中这些生物标志物的mRNA表达。在内窥镜臂，我将确定这组生物标志物单独或联合是否比单独细胞学诊断更敏感或特异性，以及表达水平是否因分期和手术可切除性而变化。血清、血浆、胰液和胆汁将被收集和储存，形成一个生物储存库，以预测未来验证基于血清或胰液的胰腺肿瘤生物标志物。我的职业目标是成为一名专注于胰腺癌生物标志物的独立转化研究者。这次培训经费是为了释放我的时间，在有成就的导师的指导下，进行分子诊断技术的培训和验证试验的设计和实施经验。我将参加生物标志物开发和验证以及生物储存库创建的课程。我将招募患者，并亲自收集和分析获得的标本。完成这项提案将使我能够实现我的职业目标，成为一名独立的转化科学家，将癌变机制和生物标志物发现技术应用于胰腺癌的早期诊断和风险评估。这样的研究有望降低与这种疾病相关的死亡率。

项目成果

Reliable gene expression measurements from fine needle aspirates of pancreatic tumors: effect of amplicon length and quality assessment.

胰腺肿瘤细针抽吸物的可靠基因表达测量：扩增子长度和质量评估的影响。

• DOI: 10.2353/jmoldx.2010.090107
• 发表时间: 2010
• 期刊: The Journal of molecular diagnostics : JMD
• 作者: Anderson,MichelleA;Brenner,DeanE;Scheiman,JamesM;Simeone,DianeM;Singh,Nalina;Sikora,MatthewJ;Zhao,Lili;Mertens,AmyN;Rae,JamesM
• 通讯作者: Rae,JamesM