Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature

被引：70

作者：

Tang, Yuhui ^{[1
]}

Tian, Wenwen ^{[1
]}

Xie, Jindong ^{[1
]}

Zou, Yutian ^{[1
]}

Wang, Zehao ^{[1
]}

Li, Ning ^{[1
]}

Zeng, Yan ^{[1
]}

Wu, Linyu ^{[1
]}

Zhang, Yue ^{[1
]}

Wu, Song ^{[1
]}

Xie, Xiaoming ^{[1
]}

Yang, Lu ^{[2
]}

机构：

[1] Sun Yat Sen Univ, Canc Ctr, Dept Breast Oncol, Collaborat Innovat Ctr Canc Med,State Key Lab Onc, Guangzhou, Peoples R China

[2] Guangdong Prov Peoples Hosp, Canc Ctr, Dept Radiotherapy, Guangzhou, Peoples R China

来源：

FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷

基金：

中国国家自然科学基金;

关键词：

fatty acid metabolism; breast cancer; prognostic signature; tumor immune microenvironment; immunotherapy; therapy resistance; REGULATORY T-CELLS; DIFFERENTIAL EXPRESSION; BETA-OXIDATION; FIBROBLASTS; RECEPTOR; MODELS;

D O I：

10.3389/fimmu.2022.843515

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Fatty acid metabolism has been deciphered to augment tumorigenesis and disease progression in addition to therapy resistance via strengthened lipid synthesis, storage, and catabolism. Breast cancer is strongly associated with the biological function of fatty acid metabolism owing to the abundant presence of adipocytes in breast tissue. It has been unraveled that tumor cells exhibit considerable plasticity based on fatty acid metabolism, responding to extra-tumoral and a range of metabolic signals, in which tumor microenvironment plays a pivotal role. However, the prognostic significance of fatty acid metabolism in breast cancer remains to be further investigated. Alongside these insights, we retrieved 269 reliable fatty acid metabolism-related genes (FMGs) and identified the landscape of copy number variations and expression level among those genes. Additionally, 11 overall survival-related FMGs were clarified by univariate Cox hazards regression analysis in The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Subsequently, a prognostic signature based on 6 overall survival (OS)-related FMGs was generated using Lasso Cox hazards regression analysis in TCGA dataset and was validated in two external cohorts. The correlation between the signature and several essential clinical parameters, including T, N, and PAM50 subtypes, was unveiled by comparing the accumulating signature value in various degrees. Furthermore, an optimal nomogram incorporating the signature, age, and American Joint Committee on Cancer (AJCC) stage was constructed, and the discrimination was verified by C-index, the calibration curve, and the decision curve analysis. The underlying implications for immune checkpoints inhibitors, the landscape of tumor immune microenvironment, and the predictive significance in therapy resistance to diverse strategies were depicted ultimately. In conclusion, our findings indicate the potential prognostic connotation of fatty acid metabolism in breast cancer, supporting novel insights into breast cancer patients' prognosis and administrating effective immunotherapy.

引用

页数：17

共 68 条

[1] Discrimination and Calibration of Clinical Prediction Models Users' Guides to the Medical Literature [J].