[5-25]Sub-classification and oncogenic network analysis of ALDH1A3-positive pancreatic ductal adenocarcinoma

报告题目：Sub-classification and oncogenic network analysis of ALDH1A3-positive pancreatic ductal adenocarcinoma

报 告 人：孔波，医学和生命科学博士 (MD, Ph.D.)

 慕尼黑工业大学附属伊萨右岸医院外科医生

 胰腺癌研究组组长

主 持 人：邓益斌 副教授

报告时间：2018年5月25日（周五）下午2：30

报告地点：苏州大学独墅湖校区云轩楼1323会议室

个人简介：

孔波，1981年10月出生，医学和生命科学博士 (MD, Ph.D.)，慕尼黑工业大学附属伊萨右岸医院外科医生并担任胰腺癌研究组组长，自2016年兼职担任南京大学医学院附属鼓楼医院消化病研究所副所长。近年来在Cancer Cell、Gut、Nature Reviews Gastroenterology & Hepatology 和 Oncogene等国际刊物上发表多篇学术论文。迄今已在胰腺研究领域发表临床和基础研究SCI论文30余篇累计影响因子超过250分，长期以来主要从事胰腺癌的基础，临床以及转化医学的工作。

报告摘要：

Pancreatic ductal adenocarcinoma (PDAC) is a histopathologically defined tumor entity with devastating prognosis. A number of clinically relevant molecular subtypes have already been identified. One squamous subtype also known as quasi-mesenchymal subtype (QM-PDA) contributes particularly to the dismal mortality rates of PDAC. However, the clinical outcome of squamous (QM-PDA) subtype is still heterogeneous and subtyping of squamous (QM-PDA) subtype is necessary to offer more concise patient stratification. Using a reverse-translational approach, we previously defined a highly aggressive PDAC subtype labeled by ALDH1A3 (aldehyde dehydrogenase 1 family member A3) expression. Furthermore, ALDH1A3-positive PDAC was found to be partially overlapping with a previously defined squamous (QM-PDA) subtype. Application of 2-mean clustering for ALDH1A3 expression across microarray datasets for cell lines, patient-derived xenograft (PDX), and micro-dissected tumor tissues identified eight subtype-specific markers. Based on dynamic transcriptional data generated from a small-scale lentiviral shRNA library, we constructed an oncogenic network from these eight markers. Our analysis revealed five mutually promotive interactions between ALDH1A3 and network components which can potentially be used to sub-classify ALDH1A3-positive PDAC. In vivo functional relevance of mutual promotions and network dynamics under different targeted pharmaceutical inhibition was explored to develop potential combination therapies specific for this subtype.