必需氨基酸缺乏是一种潜在的乳腺癌治疗策略。

Essential amino acids deprivation is a potential strategy for breast cancer treatment.

机构信息

Department of Breast Cancer Center, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, 127 Dongming Road, Zhengzhou, 450008, China.

出版信息

Breast. 2022 Apr;62:152-161. doi: 10.1016/j.breast.2022.02.009. Epub 2022 Feb 20.

DOI:10.1016/j.breast.2022.02.009

PMID:35217381

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8873954/

Abstract

AIMS

The study aimed to search novel, simple and practical index reflecting the level of essential amino acids (EAAs) metabolism in breast cancer (BC), as well as to explore the effect of enhanced EAAs metabolism on the prognosis and immune microenvironment of BC, thus providing new evidence for the application of EAAs deprivation in the BC treatment.

METHODS

The study includes the analysis of multi-omics and clinical data of 13 BC cell lines and 2898 BC patients in the public database. Further validation was performed using multi-omics and immunohistochemistry data from 83 BC tissue samples collected at our hospital.

RESULTS

According to the multi-omics data, the SLC7A5 to SLC7A8 Ratio (SSR) score was found to be significantly correlated with the EAAs level and EAAs-metabolic activity of BC, suggesting that the SSR score might be used as a biomarker to assess the degree of EAAs metabolism in BC. Besides, BC patients with high EAAs metabolism had shorter overall survival (OS) time, higher PD-L1 expression, and higher T regulatory cells (Tregs) infiltration, indicating that a high EAAs metabolism was related to a poor prognosis and immune suppression in BC. Additionally, MYC amplification is a critical molecular process in the metabolic reprogramming of EAAs in BC.

CONCLUSION

EAAs may be a possible therapeutic target for BC treatment.

摘要

目的

本研究旨在寻找反映乳腺癌（BC）必需氨基酸（EAAs）代谢水平的新型、简单且实用的指标，并探讨增强 EAAs 代谢对 BC 预后和免疫微环境的影响，从而为 EAAs 剥夺在 BC 治疗中的应用提供新的证据。

方法

本研究纳入了公共数据库中 13 个 BC 细胞系和 2898 名 BC 患者的多组学和临床数据，并进一步使用我院收集的 83 个 BC 组织样本的多组学和免疫组化数据进行了验证。

结果

根据多组学数据，发现 SLC7A5 到 SLC7A8 比值（SSR）评分与 BC 中 EAAs 水平和 EAAs 代谢活性显著相关，表明 SSR 评分可作为评估 BC 中 EAAs 代谢程度的生物标志物。此外，EAAs 代谢较高的 BC 患者总生存期（OS）更短，PD-L1 表达更高，T 调节细胞（Tregs）浸润更多，表明高 EAAs 代谢与 BC 预后不良和免疫抑制有关。此外，MYC 扩增是 BC 中 EAAs 代谢重编程的关键分子过程。