The Influence of the Amino Acid Transporter LAT1 on Patient Prognosis and the Relationships between Tumor Immunometabolic and Proliferative Features Depend on Menopausal Status in Breast Cancer

Abstract

AbstractL-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 measured18F-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.