Identification of an Aging-Related Gene Signature in Predicting Prognosis and Indicating Tumor Immune Microenvironment in Breast Cancer

被引:12
|
作者
Lv, Wenchang [1 ]
Zhao, Chongru [1 ]
Tan, Yufang [1 ]
Hu, Weijie [1 ]
Yu, Honghao [1 ]
Zeng, Ning [1 ]
Zhang, Qi [1 ]
Wu, Yiping [1 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Plast & Cosmet Surg, Wuhan, Peoples R China
来源
FRONTIERS IN ONCOLOGY | 2021年 / 11卷
关键词
breast cancer; aging-related genes; risk score; tumor immune microenvironment; prognosis; RISK SIGNATURE;
D O I
10.3389/fonc.2021.796555
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Breast cancer (BC) is the most commonly diagnosed malignancy accompanied by high invasion and metastasis features. Importantly, emerging studies have supported that aging is a key clue that participates in the immune state and development of BC. Nevertheless, there are no studies concerning the aging-related genes (AGs) in constructing the prognosis signature of BC. Here, to address this issue, we initially performed a systematic investigation of the associations between AGs and BC prognosis and accordingly constructed a prognosis risk model with 10 AGs including PLAU, JUND, IL2RG, PCMT1, PTK2, HSPA8, NFKBIA, GCLC, PIK3CA, and DGAT1 by using the least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis. Meanwhile, our analysis further confirmed that the nomogram possessed a robust performance signature for predicting prognosis compared to clinical characteristics of BC patients, including age, clinical stage, and TNM staging. Moreover, the risk score was confirmed as an independent prognostic index of BC patients and was potentially correlated with immune scores, estimate score, immune cell infiltration level, tumor microenvironment, immunotherapy effect, and drug sensitivity. Furthermore, in the external clinical sample validation, AGs were expressed differentially in patients from different risk groups, and tumor-associated macrophage markers were elevated in high-risk BC tissues with more co-localization of AGs. In addition, the proliferation, transwell, and wound healing assays also confirmed the promoting effect of DGAT1 in BC cell proliferation and migration. Therefore, this well-established risk model could be used for predicting prognosis and immunotherapy in BC, thus providing a powerful instrument for combating BC.
引用
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页数:20
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