Systematic Analysis of the Aberrances and Functional Implications of Ferroptosis in Cancer
Zekun Liu,
Qi Zhao,
Zhi-Xiang Zuo,
Shu-Qiang Yuan,
Kai Yu,
Qingfeng Zhang,
Xiaolong Zhang,
Hui Sheng,
Huai-Qiang Ju,
Han Cheng,
Feng Wang,
Rui-Hua Xu,
Ze-Xian Liu
Affiliations
Zekun Liu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Qi Zhao
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, China
Zhi-Xiang Zuo
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Shu-Qiang Yuan
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Kai Yu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Qingfeng Zhang
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Xiaolong Zhang
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Hui Sheng
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Huai-Qiang Ju
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Han Cheng
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China
Feng Wang
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
Rui-Hua Xu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, China; Corresponding author
Ze-Xian Liu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; Precision Diagnosis and Treatment for Gastrointestinal Cancer, Chinese Academy of Medical Sciences, Guangzhou 510060, China; Corresponding author
Summary: Ferroptosis is a type of cell death related to cancer; however, the characteristics of ferroptosis in cancers are still uncertain. Based on the data in The Cancer Genome Atlas, we found that most ferroptosis regulator genes (FRGs) were differentially expressed in tumors, somatic copy number alterations (SCNA) and DNA methylation contributed to their aberrant expression. We established the ferroptosis potential index (FPI) to reveal the functional roles of ferroptosis and noticed that the FPI was higher in tumors than in normal tissues in most cancers and was associated with subtypes and clinical features. The FPI was negatively correlated with several metabolic pathways but positively associated with several important metastasis-related pathways and immune-related pathways. High FPI predicted poor prognosis in several tumors, whereas FPI and FRGs impacted drug sensitivity. Our study presents a systematic analysis of ferroptosis and its regulatory genes and highlights the potential of ferroptosis-based cancer therapy.
