Biomarker validation for intraductal papillary mucinous neoplasms of the pancreas

胰腺导管内乳头状粘液性肿瘤的生物标志物验证

• 批准号: 8761860
• 负责人: Peter J Allen
• 金额: $ 49.34万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8761860
• 关键词: Adjuvant; Antibodies; Biological Markers; Blinded; Cancer Patient; Carcinoma; Characteristics; Clinical; Cyst Fluid; Cystic Neoplasm; Data Set; Databases; Development; Diagnosis; Diagnostic; Disease; Double-Blind Method; Duct (organ) structure; Dysplasia; Emotional; Enrollment; Evaluation; Excision; Failure; Financial cost; Gelatinase B; General Hospitals; Goals; Imaging technology; Institution; Interleukin-4; Intervention; Laboratories; Lesion; Life; Logistic Regressions; MMP9 gene; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of pancreas; Massachusetts; Measures; Modeling; Molecular; Mucinous Neoplasm; Nomograms; Operative Surgical Procedures; Pancreas; Pancreatectomy; Pancreatic Cyst; Papillary; Pathologic; Patients; Performance; Probability; Proteins; Research; Resected; Risk; Sampling; Screening for cancer; Stage at Diagnosis; Staging; Systemic Therapy; Technology; Testing; Therapeutic; Validation; base; clinical care; clinical decision-making; experience; high risk; improved; indexing; operation; prospective; public health relevance; research study; screening; standard of care

DESCRIPTION (provided by applicant): A critical component to successful cancer screening is the identification of a lesion for which intervention will result in prolonged survival or cure.The five-year survival of patients with resected stage IA pancreas cancer (the earliest identifiable lesion and <1% of all pancreatic cancer) is approximately 35%. Because of this, current screening paradigms for pancreatic cancer will continue to fail until a curable pancreatic cancer can be identified or until better systemic therapies can be developed. Intraductal papillary mucinous neoplasms (IPMN) of the pancreas are cystic tumors that represent the only radiographically identifiable precursor lesion of pancreatic cancer and represent an opportunity for intervention prior to the development of pancreatic cancer. Current laboratory, endoscopic, and imaging technologies are unable to distinguish between IPMN that is at low-risk (low-grade dysplasia) or at high-risk (high-grade dysplasia) of becoming malignant. Because of this, clinical decision making is very controversial and markers of high-risk disease are needed. The goal of this multi-institutional research effort is to (specific aim #1) validate a group of protein marker (MMP9, IL-4, sFASL, CA72.4) that we have found to be highly reliable in identifying high- risk IPMN. Recent analyses have identified two separate models of protein markers (sFASL/IL-4 and MMP9/CA72.4) that by themselves had accuracy rates (AUC) of 86% for high-risk disease. We will validate these markers on a multi-institutional set of cyst fluid samples (n=150) utilizing antibody bead array. We will then incorporate these markers (specific aim #2) into a recently developed preoperative prediction model (nomogram) based on clinical and radiographic factors. This model will be developed from a multi- institutional dataset developed by the three participating institutions. This molecular-clinicopathologic nomogram will then be validated (specific aim #3) on a large group of patients enrolled into a prospective multi-institutional tria. The value of identifying markers of high-risk dysplasia in patients with IPMN cannot be overstated. Development of a preoperative test to accurately discriminate between low-risk and high-risk IPMN would allow patients with high-risk lesions to undergo resection prior to the development of an incurable disease, and enable patients with low-risk lesions to avoid operation and spare them the physical, emotional, and financial costs of pancreatectomy.

描述（申请人提供）：成功癌症筛查的关键成分是鉴定干预措施会导致生存率延长或治愈的病变。切除的IA胰腺癌患者的五年生存率（最早可识别的病变，所有胰腺癌的<1％）约为35％。因此，直到可以鉴定出可治愈的胰腺癌或开发出更好的全身疗法之前，胰腺癌的当前筛查范例将继续失败。胰腺的导管内乳头粘液肿瘤（IPMN）是囊性肿瘤，代表胰腺癌的唯一射线照相前体病变，代表了在胰腺癌发展之前进行干预的机会。当前的实验室，内窥镜和成像技术无法区分低风险（低级发育不良）或高危（高级发育异常）的IPMN。因此，临床决策非常有争议，需要高危疾病的标志。这项多机构研究工作的目的是（特定目的＃1）验证一组蛋白质标记物（MMP9，IL-4，SFASL，CA72.4），我们发现它们在识别高风险IPMN方面非常可靠。最近的分析已经确定了两个单独的蛋白质标记模型（SFASL/IL-4和MMP9/CA72.4）本身的准确率（AUC）为86％，用于高危疾病。我们将在利用多机构的囊肿样品（n = 150）上验证这些标记 抗体珠阵列。然后，我们将这些标记（特定目标2）纳入基于临床和影像学因素的最近开发的术前预测模型（nom图）。该模型将从三个参与机构开发的多机构数据集开发。然后，将对入学的一大群患者进行验证该分子 - 细胞病理学戒指（特定目标＃3）。在IPMN患者中鉴定高危不典型增生的标记的价值不能被夸大。开发术前测试以准确区分低风险和高风险IPMN，将使患有高危病变的患者在发生无法治愈的疾病之前可以切除，并使低风险病变的患者避免手术并避免其身体，情感，情感和财务成本的胰腺切除术。