A Novel Ferroptosis-Related Gene Signature Predicts Overall Survival of Breast Cancer Patients

被引:22
作者
Li, Haifeng [1 ,2 ,3 ]
Li, Lu [1 ,2 ,3 ]
Xue, Cong [1 ,2 ,3 ]
Huang, Riqing [1 ,2 ,3 ]
Hu, Anqi [1 ,2 ,3 ]
An, Xin [1 ,2 ,3 ]
Shi, Yanxia [1 ,2 ,3 ]
机构
[1] Sun Yat Sen Univ, Canc Ctr, Dept Med Oncol, Guangzhou 510060, Guangdong, Peoples R China
[2] State Key Lab Oncol South China, Guangzhou 510060, Guangdong, Peoples R China
[3] Collaborat Innovat Ctr Canc Med, Guangzhou 510060, Guangdong, Peoples R China
来源
BIOLOGY-BASEL | 2021年 / 10卷 / 02期
基金
中国国家自然科学基金;
关键词
breast cancer; ferroptosis; gene signature; prognosis; immune status;
D O I
10.3390/biology10020151
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Simple Summary Ferroptosis is an iron-dependent cell death which is distinctive from common forms of cell death. Accumulating evidence indicated the close relationship between ferroptosis and numerous human diseases. Regarding breast cancer, a related study indicated that some targeted medicines could induce ferroptosis, furthermore, some basic research found that ferroptosis-related genes were closely related to breast cancer. However, the correlation between ferroptosis-related genes and breast cancer patients' prognosis remains unknown. We built an 8-ferroptosis-related-gene model to predict breast cancer patients' prognosis. This model could stratify patients into high- or low-risk groups. Additionally, tumor microenvironment analyses displayed differently enriched immune cells and immune pathways between these two groups. This 8-gene model is believed to be of great value in predicting prognosis for breast cancer patients. Breast cancer is the second leading cause of death in women, thus a reliable prognostic model for overall survival (OS) in breast cancer is needed to improve treatment and care. Ferroptosis is an iron-dependent cell death. It is already known that siramesine and lapatinib could induce ferroptosis in breast cancer cells, and some ferroptosis-related genes were closely related with the outcomes of treatments regarding breast cancer. The relationship between these genes and the prognosis of OS remains unclear. The data of gene expression and related clinical information was downloaded from public databases. Based on the TCGA-BRCA cohort, an 8-gene prediction model was established with the least absolute shrinkage and selection operator (LASSO) cox regression, and this model was validated in patients from the METABRIC cohort. Based on the median risk score obtained from the 8-gene model, patients were stratified into high- or low-risk groups. Cox regression analyses identified that the risk score was an independent predictor for OS. The findings from CIBERSORT and ssGSEA presented noticeable differences in enrichment scores for immune cells and pathways between the abovementioned two risk groups. To sum up, this prediction model has potential to be widely applied in future clinical settings.
引用
收藏
页码:1 / 15
页数:12
相关论文
共 35 条
[1]   Ferroptosis in Cancer Cell Biology [J].
Bebber, Christina M. ;
Mueller, Fabienne ;
Clemente, Laura Prieto ;
Weber, Josephine ;
von Karstedt, Silvia .
CANCERS, 2020, 12 (01)
[2]   CHAC1 degradation of glutathione enhances cystine-starvation-induced necroptosis and ferroptosis in human triple negative breast cancer cells via the GCN2-eIF2α-ATF4 pathway [J].
Chen, Meng-Shian ;
Wang, Sheng-Fan ;
Hsu, Chih-Yi ;
Yin, Pen-Hui ;
Yeh, Tien-Shun ;
Lee, Hsin-Chen ;
Tseng, Ling-Ming .
ONCOTARGET, 2017, 8 (70) :114588-114602
[3]   Modulation of G6PD affects bladder cancer via ROS accumulation and the AKT pathway in vitro [J].
Chen, Xiaoyi ;
Xu, Zhijie ;
Zhu, Zhijian ;
Chen, Anqi ;
Fu, Guanghou ;
Wang, Yimin ;
Pan, Hao ;
Jin, Baiye .
INTERNATIONAL JOURNAL OF ONCOLOGY, 2018, 53 (04) :1703-1712
[4]   A review of systematic reviews of the cost-effectiveness of hormone therapy, chemotherapy, and targeted therapy for breast cancer [J].
Diaby, Vakaramoko ;
Tawk, Rima ;
Sanogo, Vassiki ;
Xiao, Hong ;
Montero, Alberto J. .
BREAST CANCER RESEARCH AND TREATMENT, 2015, 151 (01) :27-40
[5]   Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis [J].
Dixon, Scott J. ;
Patel, Darpan ;
Welsch, Matthew ;
Skouta, Rachid ;
Lee, Eric ;
Hayano, Miki ;
Thomas, Ajit G. ;
Gleason, Caroline ;
Tatonetti, Nicholas ;
Slusher, Barbara S. ;
Stockwell, Brent R. .
ELIFE, 2014, 3
[6]  
Doll S, 2017, NAT CHEM BIOL, V13, P91, DOI [10.1038/NCHEMBIO.2239, 10.1038/nchembio.2239]
[7]   Breast cancer statistics and markers [J].
Donepudi, Mallika Siva ;
Kondapalli, Kasturi ;
Amos, Seelam Jeevan ;
Venkanteshan, Pavithra .
JOURNAL OF CANCER RESEARCH AND THERAPEUTICS, 2014, 10 (03) :506-511
[8]   Lifestyle, nutrition and breast cancer: facts and presumptions for consideration [J].
Ferrini, Krizia ;
Ghelfi, Francesca ;
Mannucci, Roberta ;
Titta, Lucilla .
ECANCERMEDICALSCIENCE, 2015, 9
[9]   Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients [J].
Fu, Junliang ;
Xu, Dongping ;
Liu, Zhenwen ;
Shi, Ming ;
Zhao, Ping ;
Fu, Baoyun ;
Zhang, Zheng ;
Yang, Huiyin ;
Zhang, Hui ;
Zhou, Chunbao ;
Ya, Jinxia ;
Jin, Lei ;
Wang, Huifen ;
Yang, Yongping ;
Fu, Yang-Xing ;
Wang, Fu-Sheng .
GASTROENTEROLOGY, 2007, 132 (07) :2328-2339
[10]   Ferroptosis in p53-dependent oncosuppression and organismal homeostasis [J].
Galluzzi, L. ;
Bravo-San Pedro, J. M. ;
Kroemer, G. .
CELL DEATH AND DIFFERENTIATION, 2015, 22 (08) :1237-1238