Lipidomic Profiling of Clinical Prostate Cancer Reveals Targetable Alterations in Membrane Lipid Composition

Cancer Res. 2021 Oct 1;81(19):4981-4993. doi: 10.1158/0008-5472.CAN-20-3863. Epub 2021 Aug 6.


Dysregulated lipid metabolism is a prominent feature of prostate cancer that is driven by androgen receptor (AR) signaling. Here we used quantitative mass spectrometry to define the "lipidome" in prostate tumors with matched benign tissues (n = 21), independent unmatched tissues (n = 47), and primary prostate explants cultured with the clinical AR antagonist enzalutamide (n = 43). Significant differences in lipid composition were detected and spatially visualized in tumors compared with matched benign samples. Notably, tumors featured higher proportions of monounsaturated lipids overall and elongated fatty acid chains in phosphatidylinositol and phosphatidylserine lipids. Significant associations between lipid profile and malignancy were validated in unmatched samples, and phospholipid composition was characteristically altered in patient tissues that responded to AR inhibition. Importantly, targeting tumor-related lipid features via inhibition of acetyl-CoA carboxylase 1 significantly reduced cellular proliferation and induced apoptosis in tissue explants. This characterization of the prostate cancer lipidome in clinical tissues reveals enhanced fatty acid synthesis, elongation, and desaturation as tumor-defining features, with potential for therapeutic targeting. SIGNIFICANCE: This study identifies malignancy and treatment-associated changes in lipid composition of clinical prostate cancer tissues, suggesting that mediators of these lipidomic changes could be targeted using existing metabolic agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Computational Biology / methods
  • Energy Metabolism
  • Humans
  • Lipid Metabolism* / drug effects
  • Lipidomics* / methods
  • Male
  • Membrane Lipids / metabolism*
  • Metabolomics / methods
  • Molecular Targeted Therapy
  • Neoplasm Grading
  • Neoplasm Staging
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / etiology
  • Prostatic Neoplasms / metabolism*
  • Spectrometry, Mass, Electrospray Ionization
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Tandem Mass Spectrometry
  • Transcriptional Regulator ERG / genetics
  • Transcriptional Regulator ERG / metabolism


  • Biomarkers
  • ERG protein, human
  • Membrane Lipids
  • Transcriptional Regulator ERG