The association between the amino acid transporter LAT1, tumor immunometabolic and proliferative features and menopausal status in breast cancer

PLoS One. 2023 Oct 11;18(10):e0292678. doi: 10.1371/journal.pone.0292678. eCollection 2023.

Abstract

L-type Amino Acid Transporter 1 (LAT1) facilitates the uptake of specific essential amino acids, and due to this quality, it has been correlated to worse patient outcomes in various cancer types. However, the relationship between LAT1 and various clinical factors, including menopausal status, in mediating LAT1's prognostic effects remains incompletely understood. This is particularly true in the unique subset of tumors that are both obesity-associated and responsive to immunotherapy, including breast cancer. To close this gap, we employed 6 sets of transcriptomic data using the Kaplan-Meier model in the Xena Functional Genomics Explorer, demonstrating that higher LAT1 expression diminishes breast cancer patients' survival probability. Additionally, we analyzed 3'-Deoxy-3'-18F-Fluorothymidine positron emission tomography-computed tomography (18F-FLT PET-CT) images found on The Cancer Imaging Archive (TCIA). After separating all patients based on menopausal status, we correlated the measured 18F-FLT uptake with various clinical parameters quantifying body composition, tumor proliferation, and immune cell infiltration. By analyzing a wealth of deidentified, open-access data, the current study investigates the impact of LAT1 expression on breast cancer prognosis, along with the menopausal status-dependent associations between tumor proliferation, immunometabolism, and systemic metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Large Neutral Amino Acid-Transporter 1 / genetics
  • Menopause
  • Positron Emission Tomography Computed Tomography
  • Positron-Emission Tomography / methods
  • Prognosis

Substances

  • Large Neutral Amino Acid-Transporter 1

Grants and funding

The authors are grateful for awards from the Lion Heart Foundation and from the Yale Cancer Center (both to R.J.P.), which supported this research. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.