Talk title: A glimpse of CNHPP: A proteomic landscape of diffuse-type gastric cancer
Dr. Jun Qin is among the few people in the world, who can integrate MS instrument design, proteomic method development, bioinformatics, biology and clinical applications into one research program. He made multiple contributions to the field of DNA damage response and nuclear hormone action by isolation and identification of endogenous protein complexes, identification of in vivo post-translational modifications and elucidation of their functional significance. As an important part of our research, he is continuously developing novel MS-based proteomic methods to analyze dynamic changes of complex biological processes in a quantitative manner. He has a long standing interest on a concept of “network analysis proteomics.” Proteins tend to assemble into multi-subunit protein complexes as the minimal biologically functional units. The execution of biological processes in the cell can be viewed as a network of ordered interactions between different protein complexes, benefits the understanding of the basic mechanisms of cellular homeostasis and pathogenesis. Specifically, he analyzed the endogenous protein complexome by immunoprecipitation (IP) with primary antibody and mass spectrometry and constructed a complete human protein interactome. He is interested in understanding several intriguing biological processes, with a special emphasis on the development and application of cutting-edge mass spectrometry-based proteomics toolkits to untangle challenging biological problems.
Abstract: A glimpse of CNHPP: A proteomic landscape of diffuse-type gastric cancer
1 State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine; National Center for Protein Sciences (The PHOENIX center, Beijing), Beijing 102206, China
2 Center for Molecular Discovery, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
China is at the leading edge of catching the wave of rapid development in proteomics. Chinese Human Proteome Project (CNHPP) is a large undertaking at dissection of the proteomic landscape of cancer. Diffuse-type gastric cancer (DGC) accounts for 30% of Gastric cancer (GC), with the worse clinical outcomes. Here we describe the first proteomic landscape of diffuse-type gastric cancer. Based on proteome profiling data of 84 DGC samples, DGC can be subtyped into 3 major classes that exhibit distinct proteome features. Importantly, the 3 subtypes are correlated with distinct clinical outcomes and adjuvant chemotherapy effect. To facilitate potential clinical applications, we further developed a simplified classifier, which is able to distinguish three DGC subtypes with 7 protein markers. Integrated analysis of proteome and targeted exome sequencing data revealed a loose connection between the genome and the proteome. It is striking that for many mutational cancer driver genes, their gene products were never detected in the gastric proteome, which raises a serious concern about using DNA sequencing to predict protein expression and highlights the necessity of measuring proteins directly for precision medicine. We also nominated several druggable candidates for developing therapy against DSG based on the altered DGC proteome and the association with patients’ overall survival.