Proteogenomic landscape of human pancreatic ductal adenocarcinoma in an Asian population reveals tumor cell-enriched and immune-rich subtypes.

Autor: Hyeon DY; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea., Nam D; Department of Chemistry and Center for Proteogenome Research, Korea University, Seoul, Republic of Korea., Han Y; Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea., Kim DK; Department of Anatomy and Cell Biology and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.; Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Seoul, Republic of Korea., Kim G; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.; Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul, Republic of Korea., Kim D; Department of Biological Sciences, College of Natural Sciences and Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea., Bae J; Department of Chemistry and Center for Proteogenome Research, Korea University, Seoul, Republic of Korea., Back S; Department of Chemistry and Center for Proteogenome Research, Korea University, Seoul, Republic of Korea., Mun DG; Department of Chemistry and Center for Proteogenome Research, Korea University, Seoul, Republic of Korea., Madar IH; Department of Chemistry and Center for Proteogenome Research, Korea University, Seoul, Republic of Korea., Lee H; Department of Chemistry and Center for Proteogenome Research, Korea University, Seoul, Republic of Korea., Kim SJ; Department of Chemistry and Center for Proteogenome Research, Korea University, Seoul, Republic of Korea., Kim H; Department of Chemistry and Center for Proteogenome Research, Korea University, Seoul, Republic of Korea., Hyun S; Department of Biological Sciences, College of Natural Sciences and Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea., Kim CR; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.; Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul, Republic of Korea., Choi SA; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.; Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul, Republic of Korea., Kim YR; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.; Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul, Republic of Korea., Jeong J; Department of Anatomy and Cell Biology and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea., Jeon S; Department of Anatomy and Cell Biology and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea., Choo YW; Department of Anatomy and Cell Biology and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea., Lee KB; Department of Pathology, Seoul National University College of Medicine, Seoul, Korea., Kwon W; Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea., Choi S; Department of Computer Science, Hanyang University, Seoul, Republic of Korea., Goo T; Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea., Park T; Department of Statistics, Seoul National University, Seoul, Republic of Korea., Suh YA; Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea., Kim H; Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea., Ku JL; Korean Cell Line Bank, Laboratory of Cell Biology, Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea., Kim MS; Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu, Republic of Korea., Paek E; Department of Computer Science, Hanyang University, Seoul, Republic of Korea., Park D; Department of Biological Sciences, College of Natural Sciences and Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea. dpark@ajou.ac.kr., Jung K; Department of Anatomy and Cell Biology and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. keehoon.jung@snu.ac.kr.; Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea. keehoon.jung@snu.ac.kr., Baek SH; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea. sbaek@snu.ac.kr.; Creative Research Initiatives Center for Epigenetic Code and Diseases, Seoul National University, Seoul, Republic of Korea. sbaek@snu.ac.kr., Jang JY; Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea. jangjy4@snu.ac.kr., Hwang D; School of Biological Sciences, Seoul National University, Seoul, Republic of Korea. daehee@snu.ac.kr., Lee SW; Department of Chemistry and Center for Proteogenome Research, Korea University, Seoul, Republic of Korea. sw_lee@korea.ac.kr.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2023 Feb; Vol. 4 (2), pp. 290-307. Date of Electronic Publication: 2022 Dec 22.
DOI: 10.1038/s43018-022-00479-7
Abstrakt: 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.
(© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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