Fingerprinting the Metabolic and Lipidomic Landscapes of Pancreatic Ductal Adenocarcinoma With MALDI Imaging.

Details

• Alternative Title:
  Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 2026, v. 32, no. 15: Fingerprinting the Metabolic and Lipidomic Landscapes of Pancreatic Ductal Adenocarcinoma With MALDI Imaging.
• Journal Article:
  Clinical Cancer Research : An Official Journal of the American Association for Cancer Research
• Personal Author:
  Yousf, Saleem ; Glunde, Kristine ; Brown, Dalton R. ; Tressler, Caitlin ; Solaiyappan, Meiyappan ; Krishnamachary, Balaji ; Mironchik, Yelena ; Dbouk, Mohamad ; Goggins, Michael G. ; Bhujwalla, Zaver M.
• Description:
  Metabolic reprogramming plays an integral role in progression, immune evasion, and response to treatment in many cancers, including pancreatic ductal adenocarcinoma (PDAC). This study aimed to spatially characterize the metabolic and lipidomic alterations in PDAC and its precursor lesion, intraductal papillary mucinous neoplasm (IPMN), compared with normal/nonneoplastic pancreatic tissue.
  
  Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was employed to perform spatial metabolic and lipidomic profiling of human PDAC, IPMN, and normal/nonneoplastic pancreatic tissues. MALDI-MSI provided multiplexed metabolic images of tissue samples at 200 μm resolution, allowing spatial characterization of the tumor metabolic landscape.
  
  Our data identified metabolic signatures characteristic of PDAC, with several of these altered in IPMN compared with normal/nonneoplastic tissue. The metabolic fingerprint of PDAC was characterized by increased levels of taurine, ascorbic acid, and a variety of lipid species, including most of the phosphatidylcholines (PC) and sphingomyelins compared with normal/nonneoplastic pancreas tissue, alongside elevated acetylcarnitine, butyrylcarnitine, and PC (PC 34:3) relative to IPMN; significant reductions were observed in creatine, malate, and lysophosphatidylcholine (LPC 16:0). In contrast, IPMN tissues demonstrated a significant reduction of xanthine, arginine, and tryptophan compared with normal/nonneoplastic pancreas tissue. These metabolic signatures were spatially heterogeneous.
  
  Our findings provide novel insights into the metabolic and lipidomic underpinnings of PDAC. Metabolic alterations in PDAC were associated with proliferation, immune evasion, and treatment resistance.
• Content Notes:
  Author manuscript
• Subjects:
  • Humans
  • Carcinoma, Pancreatic Ductal
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Pancreatic Neoplasms
  • Lipidomics
  • Female
  • Male
  • Metabolomics
  • Metabolome
  • Middle Aged
  More +
• Keywords:
  • PDAC
  • IPMN
  • pancreatic tissue
  • MALDI-MSI
  • metabolomics
  • lipidomics
• Source:
  Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, 2026, v. 32, no. 15
• DOI:
  https://doi.org/10.1158/1078-0432.CCR-25-1115
• ISSN:
  1078-0432 ; 1557-3265
• Pubmed ID:
  42043783
• Pubmed Central ID:
  PMC13200568
• Document Type:
  Text
• Funding:
  R35 CA209960/CA/NCI NIH HHSUnited States/ ; R01 CA281075/CA/NCI NIH HHSUnited States/ ; P30 CA006973/CA/NCI NIH HHSUnited States/ ; R01 CA193365/CA/NCI NIH HHSUnited States/ ; U01 CA210170/CA/NCI NIH HHSUnited States/ ; S10 OD030500/OD/NIH HHSUnited States/ ; R01CA281075/National Cancer Institute (NCI)/ ; R35CA209960/National Cancer Institute (NCI)/ ; P30CA006973/National Cancer Institute (NCI)/ ; R01CA193365/National Cancer Institute (NCI)/ ; U01CA210170/National Cancer Institute (NCI)/ ; S10 OD030500/CD/ODCDC CDC HHSUnited States/
• Genre:
  Journal Article
• Pages in Document:
  3325-3337 (24 pdf pages)
• Volume:
  32
• Issue:
  15
• Download URL:
  https://stacks.cdc.gov/view/cdc/260676/cdc_260676_DS1.pdf
• File Type:
  [PDF - 3.04 MB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:7714da465ddd99a9ed9edd5713f231c727033eb442c140367c61a857b6e6a91c618eceaf85a0a5eb58a0c3e3afe00d5aa2b28b852214b76ac3c74b67d69892c0