1. Proteogenomic Characterization of Human Pancreatic Cancer
- Author
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Eunok Paek, Jingi Bae, Do Young Hyeon, Jin-Young Jang, Suwan Jeon, Wooil Kwon, Daehee Hwang, Hongbeom Kim, Gi Beom Kim, Hokeun Kim, Su Jin Kim, Kyung Bun Lee, Ja-Lok Ku, Seunghoon Back, Seunghyuk Choi, Dong-Gi Mun, Juhee Jeong, Chang Rok Kim, Hangyeore Lee, Daechan Park, Sung Hee Baek, Sangyeop Hyun, Youngmin Han, Daeun Kim, Sang Won Lee, Min-Sik Kim, Young Ah Suh, Dowoon Nam, Keehoon Jung, Inamul Hasan Madar, Duk Ki Kim, and Yeon Woong Choo
- Subjects
Messenger RNA ,Immune system ,medicine.anatomical_structure ,Oncogene ,Somatic cell ,Pancreatic cancer ,T cell ,medicine ,Cancer research ,Phosphorylation ,Signal transduction ,Biology ,medicine.disease - Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with poor prognosis, and the situation has not improved despite extensive clinical and scientific research. Here, we report proteogenomic analysis of PDAC. Mutation-phosphorylation correlations identified signaling pathways associated with somatic mutations in significantly mutated genes. mRNA-protein abundance correlations revealed oncogene and tumor suppressor candidates correlating with patient survival. Integrated clustering of mRNA, protein, and phosphorylation data identified six PDAC subtypes (Sub1-6), which were indistinguishable using mRNA data alone. mRNA and protein signatures defining Sub1-6 revealed that Sub1, Sub2-4, and Sub5-6 were precursor, invasive, and immunogenic tumors, respectively. In the Sub2-4 group, proliferation was highest for Sub4; Sub6 in the Sub5-6 group had an increased pancreatic secretion capacity. Orthotopic mouse PDAC models revealed higher numbers of pro-tumorigenic immune cells in Sub4 tumors, inhibiting T cell proliferation. Our proteogenomic analysis provides therapeutic targets and improves understanding of cancer biology and patient stratification in PDAC.
- Published
- 2020
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