Molecular characterization of precursor lesions of bile duct cancer

胆管癌前驱病变的分子特征

• 批准号: 284318716
• 负责人: Professorin Dr. Irene Esposito
• 金额: --
• 依托单位: Institut für Pathologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/284318716?language=en
• 关键词: Molecular; characterization; precursor; lesions; bile

Bile duct cancer (cholangiocarcinoma) is a dismal disease with limited treatment options that is mostly detected at late stages. Recent studies show that tumor progression follows an adenoma-carcinoma sequence and non-invasive precursor lesions of bile duct cancer exist. However, the molecular carcinogenesis and the prognostic value of non-invasive precursor lesions remain largely unclear.The overall goal of this research project is to investigate the molecular changes that follow the progression from non-invasive lesions to invasive carcinoma in a systematic approach and to test the hypothesis that distinct pathways in the carcinogenesis of biliary cancer exist.The specific aims are (I) to assemble and characterize a large sample collection of bile duct cancer (cholangiocarcinoma) and its precursor lesions, (II) to characterize the multistep carcinogenesis of cholangiocarcinoma in a systematic approach with focus on (lI.l) the characterization of molecular changes of common oncogenic pathways and candidate genes during progression from non-invasive lesions (BilIN, IPNB and ITPN) to invasive cholangiocarcinoma (CCC) and (lI.ll) the identification of unknown candidate genes that follow the progression from non-invasive lesions (BilIN, IPNB and ITPN) to invasive cholangiocarcinoma (CCC), (llI) to characterize the subsequent changes in protein expression during the tumor progression and (IV) to compare the results of aims II-III to pancreatic carcinogenesis with special emphasis on PanIN and gastric IPMN. Eventually, a detailed characterization of precursor lesions of bile duct cancer will provide new insights in the pathogenesis of bile duct cancer and may help to improve diagnosis, treatment and risk stratification of patients with cholangiocarcinoma.

胆管癌（胆管癌）是一种令人沮丧的疾病，治疗选择有限，大多在晚期发现。最近的研究表明，肿瘤的进展遵循腺瘤-癌的顺序，并且存在胆管癌的非侵袭性前驱病变。然而，在这方面，非侵袭性前体病变的分子致癌作用和预后价值尚不清楚。本研究的总体目标是系统地研究从非侵袭性病变发展为侵袭性癌后的分子变化，并验证胆管癌发生中存在不同途径的假设。具体目的是：收集并鉴定大量胆管癌样本（胆管癌）及其前驱病变，（II）以系统方法描述胆管癌的多步骤癌变过程，重点是（II.l）在从非侵入性病变进展期间常见致癌途径和候选基因的分子变化的表征（BilIN、IPNB和ITPN）与浸润性胆管癌（CCC）的关系，（III. II）鉴定从非侵入性病变进展后的未知候选基因（BilIN、IPNB和ITPN）与浸润性胆管癌（CCC），（III）表征肿瘤进展期间蛋白质表达的后续变化，和（IV）比较目标II-3的结果。III胰腺癌的发生，特别强调PanIN和胃IPMN。最终，胆管癌前病变的详细表征将为胆管癌的发病机制提供新的见解，并可能有助于改善胆管癌患者的诊断，治疗和风险分层。