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L 型氨基酸转运蛋白 1(LAT1)与浸润性乳腺癌免疫系统及预后的关联

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

查看英文原题

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

PubMed 2022/02/17(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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中文摘要

L型氨基酸转运蛋白1(LAT1),也称为SLC7A5,被认为可调节肿瘤代谢并与肿瘤增殖相关。在浸润性乳腺癌中,我们从临床病理学角度研究了LAT1表达的实用性。通过免疫组织化学分析评估了250例接受长期随访的乳腺癌患者的LAT1表达。

我们评估了LAT1表达与患者预后及临床病理因素之间的关系。按LAT1表达分层的乳腺癌特异性生存率进行了评估。人表皮生长因子受体2(HER2)阳性且伴有转移的患者接受了曲妥珠单抗治疗。根据国际工作组指南评估了TIL(肿瘤浸润淋巴细胞)(TILs)的密度。

在本研究中,高LAT1表达与雌激素受体(ER)阴性、孕激素受体阴性、高组织学分级、TILs增加以及程序性死亡配体1阳性显著相关。在ER阳性和HER2阴性患者中,高LAT1是不良预后的独立指标(风险比(HR)= 2.97;95%置信区间(CI),1.16-7.62;p = 0.023)。

此外,高LAT1表达是具有侵袭性特征的luminal B样乳腺癌的独立不良预后因素(HR = 3.39;95% CI 1.35-8.52;p = 0.0094)。

总之,高LAT1表达可用于识别具有侵袭性行为和高肿瘤免疫反应的浸润性乳腺癌亚组。我们的研究结果表明,LAT1可能是乳腺癌患者的候选治疗靶点,尤其是luminal B样型乳腺癌患者。

展开英文摘要原文

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.

论文信息

作者
Kurozumi S、Kaira K、Matsumoto H、Kurosumi M、Yokobori T、Kanai Y、Sekine C、Honda C
单位
Department of Breast Surgery, International University of Health and Welfare, 852, Hatakeda, Narita, Chiba, 286-8520, Japan. skurozumi@iuhw.ac.jp.Japan
文献类型
临床试验 · 非美国政府资助研究
期刊
Scientific reports2022 Feb 17
原文标识
PubMed 35177712 · DOI 10.1038/s41598-022-06615-8