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

Abstract

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. LAT1 expression was evaluated via immunohistochemistry analyses in 250 breast cancer patients undergoing long-term follow-up. We assessed the relationships between LAT1 expression and patient outcomes and clinicopathological factors. Breast cancer-specific survival stratified by LAT1 expression was assessed. Human epidermal growth factor receptor 2 (HER2)-positive patients with metastasis received trastuzumab therapy. The density of tumor-infiltrating lymphocytes (TILs) was evaluated according to the International Working Group guidelines. In the current study, high LAT1 expression was significantly correlated with estrogen receptor (ER) negativity, progesterone receptor negativity, high histological grade, increased TILs, and programmed death ligand 1 positivity. Among the ER-positive and HER2-negative patients, 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). In conclusion, high LAT1 expression could be used to identify 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.

• Authors: Sasagu Kurozumi, Kyoichi Kaira, Hiroshi Matsumoto, Masafumi Kurosumi, Takehiko Yokobori, Yoshikatsu Kanai, Chikako Sekine, Chikako Honda, Ayaka Katayama, Mio Furuya, Sho Shiino, Takaya Makiguchi, Nigel P Mongan, Emad A Rakha, Tetsunari Oyama, Takaaki Fujii, Ken Shirabe, Jun Horiguchi
• Journal: Scientific reports (Sci Rep) Vol. 12 Issue 1 Pg. 2742 (02 17 2022) ISSN: 2045-2322 [Electronic] England
• PMID: 35177712 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• B7-H1 Antigen
• CD274 protein, human
• Large Neutral Amino Acid-Transporter 1
• SLC7A5 protein, human
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Adult
• Aged
• B7-H1 Antigen (immunology)
• Breast Neoplasms (drug therapy, immunology, mortality, pathology)
• Disease-Free Survival
• Female
• Humans
• Large Neutral Amino Acid-Transporter 1 (immunology)
• Lymphocytes, Tumor-Infiltrating (immunology)
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Receptor, ErbB-2 (metabolism)
• Survival Rate