Association of L-type amino acid transporter 1 (LAT1) with the immune system and prognosis in invasive breast cancer

Abstract

PURPOSE: L-type amino acid transporter 1 (LAT1), also referred to as SLC7A5, is believed to regulate tumor metabolism and be associated with tumor proliferation. In invasive breast cancer, we clinicopathologically investigated the utility of LAT1 expression. METHODS: LAT1 expression was evaluated via immunohistochemistry analyses in 250 breast cancer patients undergoing long-term follow-up. We assessed the relationship between LAT1 expression and the patients’ outcomes and clinicopathological factors. Breast cancer-specific survival stratified by LAT1 expression was assessed.RESULTS: High LAT1 expression was significantly correlated with estrogen receptor (ER) negativity, progesterone receptor negativity, high histological grade, increased tumor-infiltrating lymphocytes, and programmed death ligand 1 positivity. Among the ER-positive and human epidermal growth factor 2-negative type cases, high LAT1 was an independent indicator of poor outcomes (hazard ratio (HR) = 2.97; 95% confidence interval (CI), 1.16–7.62; p = 0.023). Moreover, high LAT1 expression was an independent poor prognostic factor in luminal B-like breast cancer with aggressive features (HR = 3.39; 95% CI, 1.35–8.52; p = 0.0094).CONCLUSIONS: High LAT1 expression identified a subgroup of invasive breast cancer characterized by aggressive behavior and high tumor immunoreaction. Our findings suggest that LAT1 might be a candidate therapeutic target for breast cancer patients, particularly those with luminal B-like type breast cancer.

Mechanism and application of nonessential amino acid deprivation associated with tumor therapy

“…114 Glutamine can be obtained by cells via various membrane-anchored amino acid transporters termed solute carrier transporters (SLC), several of which are overexpressed in cancer cells, like SLC1A5 (ASCT2) and SLC7A5 (LAT1). [115][116][117] Besides, under nutrient-deprived conditions, glutamine can be acquired by cancer cells through breaking down macromolecules. 118 It should also be mentioned that some certain kind of cancer cells can derive glutamine through autophagic degrading intracellular proteins.…”

“…Yet, some rapidly proliferating cells rely on an exogenous supply of glutamine for its increase in demand 114 . Glutamine can be obtained by cells via various membrane‐anchored amino acid transporters termed solute carrier transporters (SLC), several of which are overexpressed in cancer cells, like SLC1A5 (ASCT2) and SLC7A5 (LAT1) 115–117 . Besides, under nutrient‐deprived conditions, glutamine can be acquired by cancer cells through breaking down macromolecules 118 .…”

Accuracy and Utility of Preoperative Ultrasound-Guided Axillary Lymph Node Biopsy for Invasive Breast Cancer: A Systematic Review and Meta-Analysis

“…e grading and staging of breast cancer has a significant impact on prognosis [22,23]. e WHO takes the Nottingham grading system as the standard histological grading system for invasive breast cancer [24,25]. e evaluation indicators are the proportion of glandular duct formation, nuclear pleomorphism, and mitotic image count [26].…”