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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Breast Cancer
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1382986
This article is part of the Research Topic Multidisciplinary and Personalized Approach in the Treatment of Advanced Breast Cancer View all 9 articles

Lipid Profiling of RON and DEK Dependent Signaling in Breast Cancer Guides Discovery of Gene Networks Predictive of Poor Outcomes Survival

Provisionally accepted
Sara Vicente-Munoz Sara Vicente-Munoz 1,2James C. Davis James C. Davis 3Andrew N. Lane Andrew N. Lane 4Susan E. Waltz Susan E. Waltz 5,6*Susanne I. Wells Susanne I. Wells 2,7*
  • 1 NMR-Metabolomics Core, Division of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
  • 2 Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States
  • 3 Department of Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH, United States
  • 4 Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY, United States
  • 5 Department of Cancer Biology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, United States
  • 6 Cincinnati Veterans Affairs Medical Center, Cincinnati, OH, United States
  • 7 Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States

The final, formatted version of the article will be published soon.

    Recurrent and metastatic breast cancer is frequently treatment resistant. A wealth of evidence suggests that reprogrammed lipid metabolism supports cancer recurrence. Overexpression of the RON and DEK oncoproteins in breast cancer is associated with poor outcome. Both proteins promote cancer metastasis in laboratory models, but their influence on lipid metabolite levels remain unknown. To measure RONand DEK-dependent steady-state lipid metabolite levels, an Nuclear Magnetic Resonance (NMR)based approach was utilized. The observed differences identified a lipid metabolism-related gene expression signature that is prognostic of overall survival (OS), distant metastasis-free survival (DMFS), post-progression survival (PPS), and recurrence-free survival (RFS) in patients with breast cancer. RON loss led to decreased cholesterol and sphingomyelin levels, while DEK loss increased total fatty acid levels and decreased free glycerol levels. Lipid-related genes were then queried to define a signature that predicts poor outcomes for patients with breast cancer patients.other cancer types. Taken together, RON and DEK differentially regulate lipid metabolism in a manner that predicts and may promote breast cancer metastasis and recurrence.

    Keywords: breast cancer, Recurrence, metastasis, RON, DEK, NMR spectroscopy, lipidomics

    Received: 06 Feb 2024; Accepted: 30 Jul 2024.

    Copyright: © 2024 Vicente-Munoz, Davis, Lane, Waltz and Wells. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Susan E. Waltz, Department of Cancer Biology, College of Medicine, University of Cincinnati, Cincinnati, 45267-0521, Ohio, United States
    Susanne I. Wells, Department of Pediatrics, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, United States

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