Proteogenomic characterization of pancreatic neuroendocrine tumors uncovers hypoxia and immune signatures in clinically aggressive subtypes Journal Article


Authors: Tanaka, A.; Ogawa, M.; Zhou, Y.; Otani, Y.; Hendrickson, R. C.; Miele, M. M.; Li, Z.; Klimstra, D. S.; Wang, J. Y.; Roehrl, M. H.
Article Title: Proteogenomic characterization of pancreatic neuroendocrine tumors uncovers hypoxia and immune signatures in clinically aggressive subtypes
Abstract: Pancreatic neuroendocrine tumors (PanNETs) represent well-differentiated endocrine neoplasms with variable clinical outcomes. Predicting patient outcomes using the current tumor grading system is challenging. In addition, traditional systemic treatment options for PanNETs, such as somatostatin analogs or cytotoxic chemotherapies, are very limited. To address these issues, we characterized PanNETs using integrated proteogenomics and identified four subtypes. Two proteomic subtypes showed high recurrence rates, suggesting clinical aggressiveness that was missed by current classification. Hypoxia and inflammatory pathways were significantly enriched in the clinically aggressive subtypes. Detailed analyses revealed metabolic adaptation via glycolysis upregulation and oxidative phosphorylation downregulation under hypoxic conditions. Inflammatory signature analysis revealed that immunosuppressive molecules were enriched in immune hot tumors and might be immunotherapy targets. In this study, we characterized clinically aggressive proteomic subtypes of well-differentiated PanNETs and identified candidate therapeutic targets. © 2024
Keywords: proteomics; genomics; cancer; cancer systems biology
Journal Title: iScience
Volume: 27
Issue: 8
ISSN: 2589-0042
Publisher: Cell Press  
Date Published: 2024-08-16
Start Page: 110544
Language: English
DOI: 10.1016/j.isci.2024.110544
PROVIDER: scopus
PMCID: PMC11350455
PUBMED: 39206147
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF; MSK corresponding author is Michael Roehrl -- Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. David S Klimstra
    978 Klimstra
  2. Michael H Roehrl
    127 Roehrl
  3. Matthew M Miele
    18 Miele
  4. Zhuoning Li
    17 Li
  5. Atsushi Tanaka
    35 Tanaka
  6. Yihua Zhou
    13 Zhou
  7. Makiko Ogawa
    26 Ogawa