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

Do Young Hyeon, Dowoon Nam, Youngmin Han, Duk Ki Kim, Gibeom Kim, Daeun Kim, Jingi Bae, Seunghoon Back, Dong Gi Mun, Inamul Hasan Madar, Hangyeore Lee, Su Jin Kim, Hokeun Kim, Sangyeop Hyun, Chang Rok Kim, Seon Ah Choi, Yong Ryoul Kim, Juhee Jeong, Suwan Jeon, Yeon Woong ChooKyung Bun Lee, Wooil Kwon, Seunghyuk Choi, Taewan Goo, Taesung Park, Young Ah Suh, Hongbeom Kim, Ja Lok Ku, Min Sik Kim, Eunok Paek, Daechan Park, Keehoon Jung, Sung Hee Baek, Jin Young Jang, Daehee Hwang, Sang Won Lee

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)290-307
Number of pages18
JournalNature Cancer
Volume4
Issue number2
DOIs
Publication statusPublished - 2023 Feb

Bibliographical note

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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