Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Proteogenomic Characterization of Human Gastric Cancer (#175)

Jianmin Wu 1 , Ludovic Gillet 2 , Tiannan Guo 2 3 , Yang Du 1 , Sijia Cui 1 , Luxi Zhang 1 , Huan Yu 1 , Lihua Cao 1 , Peng Xue 2 4 , Yi Zhu 2 3 , Yang Yang 1 , Man Wang 1 , Xiaoqing Guan 1 , Bin Dong 1 , Ying Hu 1 , Xiaofang Xing 1 , Xiangyu Gao 1 , Fei Shan 1 , Lei Tang 1 , Lianhai Zhang 1 , Zhongwu Li 1 , Xiangqian Su 1 , Aiwen Wu 1 , Zhaode Bu 1 , Ziyu Li 1 , Shuqin Jia 1 , Ruedi Aebersold 2 5 , Jiafu Ji 1
  1. Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
  2. Department of Biology, Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland
  3. School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province, China
  4. Institue of biophysics, Chinese academy of science, Beijing, China
  5. Faculty of Science , University of Zurich, Zurich, Switzerland

Gastric Cancer is the fifth most prevalent malignancy and the third leading cause of cancer death worldwide, of which more than half occurred in East Asia. Although previous genomic studies demonstrated the potential for molecular classifications of gastric cancer for personalized medicine, e.g. microsatellite Instability (MSI)-high subtype of patients showing resistant to chemotherapy, a large proportion of gastric cancer patients need further molecular investigation to develop tailored therapeutic regimen. We characterized the proteogenomic landscapes of 186 gastric cancer patients (including all Lauren classifications) by integrative analysis of genomic, transcriptomic and proteomic data. Fresh-frozen treatment-naive gastric cancer surgical samples were collected from the biobank of Peking University Cancer Hospital (2010.01-2013.06). Tumor cellularity was examined by H&E staining, and samples with tumor cellularity >=60% were selected for exome sequencing, RNA-seq and reproducible proteomic quantification, by pressure cycling technology (PCT) assisted sample preparation followed by SWATH‐MS. The mass spectrometry data were processed for consensus clustering analysis, which defined four proteomic subtypes in our cohort. We find that this molecular classification is significantly correlated with patient outcome and presents distinct molecular characteristics between subtypes. By combining genomic and proteomic features, our analysis elucidates the molecular details of gastric cancer, and identifies novel prognosis markers and therapeutic targets. Correspondence to Jianmin Wu (wujm@bjmu.edu.cn), Ruedi Aebersold (aebersold@imsb.biol.ethz.ch) and Jiafu Ji (jijiafu@hsc.pku.edu.cn).