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

Kurozumi, Sasagu; Kaira, Kyoichi; Matsumoto, Hiroshi; Kurosumi, Masafumi; Yokobori, Takehiko; Kanai, Yoshikatsu; Sekine, Chikako; Honda, Chikako; Katayama, Ayaka; Furuya, Mio; Shiino, Sho; Makiguchi, Takaya; Mongan, Nigel P.; Rakha, Emad A.; Oyama, Tetsunari; Fujii, Takaaki; Shirabe, Ken; Horiguchi, Jun

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.

• Journal Article Type: Article
• Acceptance Date: Feb 2, 2022
• Online Publication Date: Feb 17, 2022
• Publication Date: Dec 1, 2022
• Deposit Date: Feb 22, 2022
• Publicly Available Date: Feb 24, 2022
• Journal: Scientific Reports
• Electronic ISSN: 2045-2322
• Publisher: Springer Science and Business Media LLC
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 1
• Article Number: 2742
• DOI: https://doi.org/10.1038/s41598-022-06615-8
• Keywords: Multidisciplinary
• Public URL: https://nottingham-repository.worktribe.com/output/7502699
• Additional Information: Received: 1 August 2021; Accepted: 2 February 2022; First Online: 17 February 2022; : SK has received honoraria from Chugai Pharmaceutical, Ltd., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Eli Lilly and Company, MSD K.K., AstraZeneca K.K., and Novartis Japan. KK has received research grants from and is a speaker honorarium for Ono Pharmaceutical Company, Chugai Pharmaceutical, Taiho Pharmaceutical, and AstraZeneca. TY has received research grants from Ono Pharmaceutical Co., Ltd., CHUGAI Pharmaceutical Co., Ltd., and Memolead Co. KS has received research grants from CHUGAI Pharmaceutical Co., Ltd., and Ono Pharmaceutical Co., Ltd. The other authors declare that they have no conflicts of interest.