한빛사논문
- 조회676
Do Young Hyeon # 1, Dowoon Nam # 2, Youngmin Han # 3, Duk Ki Kim # 4 5, Gibeom Kim # 1 6, Daeun Kim # 7, Jingi Bae 2, Seunghoon Back 2, Dong-Gi Mun 2, Inamul Hasan Madar 2, Hangyeore Lee 2, Su-Jin Kim 2, Hokeun Kim 2, Sangyeop Hyun 7, Chang Rok Kim 1 6, Seon Ah Choi 1 6, Yong Ryoul Kim 1 6, Juhee Jeong 4, Suwan Jeon 4, Yeon Woong Choo 4, Kyung Bun Lee 8, Wooil Kwon 3, Seunghyuk Choi 9, Taewan Goo 10, Taesung Park 11, Young-Ah Suh 3, Hongbeom Kim 3, Ja-Lok Ku 12, Min-Sik Kim 13, Eunok Paek 9, Daechan Park 14, Keehoon Jung 15 16, Sung Hee Baek 17 18, Jin-Young Jang 19, Daehee Hwang 20, Sang-Won Lee 21
1School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
2Department of Chemistry and Center for Proteogenome Research, Korea University, Seoul, Republic of Korea.
3Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
4Department of Anatomy and Cell Biology and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
5Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Seoul, Republic of Korea.
6Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul, Republic of Korea.
7Department of Biological Sciences, College of Natural Sciences and Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
8Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
9Department of Computer Science, Hanyang University, Seoul, Republic of Korea.
10Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea.
11Department of Statistics, Seoul National University, Seoul, Republic of Korea.
12Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
13Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea.
14Department of Biological Sciences, College of Natural Sciences and Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
15Department of Anatomy and Cell Biology and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
16Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea.
17School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
18Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul, Republic of Korea.
19Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
20School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
21Department of Chemistry and Center for Proteogenome Research, Korea University, Seoul, Republic of Korea.
#Contributed equally.
These authors contributed equally: Do Young Hyeon, Dowoon Nam, Youngmin Han, Duk Ki Kim, Gibeom Kim, Daeun Kim.
Corresponding authors: Correspondence to Daechan Park, Keehoon Jung, Sung Hee Baek, Jin-Young Jang, Daehee Hwang or Sang-Won Lee.
Abstract
We report a proteogenomic analysis of pancreatic ductal adenocarcinoma (PDAC). Mutation–phosphorylation correlations identified signaling pathways associated with somatic mutations in significantly mutated genes. Messenger RNA–protein abundance correlations revealed potential prognostic biomarkers correlated with patient survival. Integrated clustering of mRNA, protein and phosphorylation data identified six PDAC subtypes. Cellular pathways represented by mRNA and protein signatures, defining the subtypes and compositions of cell types in the subtypes, characterized them as classical progenitor (TS1), squamous (TS2–4), immunogenic progenitor (IS1) and exocrine-like (IS2) subtypes. Compared with the mRNA data, protein and phosphorylation data further classified the squamous subtypes into activated stroma-enriched (TS2), invasive (TS3) and invasive-proliferative (TS4) squamous subtypes. Orthotopic mouse PDAC models revealed a higher number of pro-tumorigenic immune cells in TS4, inhibiting T cell proliferation. Our proteogenomic analysis provides significantly mutated genes/biomarkers, cellular pathways and cell types as potential therapeutic targets to improve stratification of patients with PDAC.
논문정보
- Research article
- 2022년 12월 (BRIC 등록일 2023-01-02)
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