Prognostic and Immunological Role of Key Genes of Ferroptosis in Pan-Cancer

Abstract

Solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), and apoptosis inducing factor mitochondria associated 2 (AIFM2) are the key regulators in ferroptosis. However, the expression patterns and prognostic roles of these genes in pan-cancer are still largely unclear. The expression patterns and prognostic roles of SLC7A11, GPX4, and AIFM2 and the relationships between the expression levels of these genes and immune infiltration levels in pan-cancer were analyzed by using TIMER, gene expression profiling interactive analysis (GEPIA), Oncomine, and Kaplan–Meier databases. Our results showed that both SLC7A11 and GPX4 were overexpressed in colorectal cancer, and SLC7A11 was overexpressed in lung cancer. High levels of SLC7A11 and AIFM2 were significantly linked with the shortened disease-free survival and overall survival (OS) in adrenocortical carcinoma (ACC), respectively. And high expression of SLC7A11, GPX4, and AIFM2 were significantly correlated with the shortened OS of acute myeloid leukemia patients. In esophageal carcinoma (ESCA), GPX4 expression was significantly associated with the infiltration of macrophage and myeloid dendritic cell, and AIFM2 expression was significantly associated with the infiltration of CD4+ T cell. Importantly, GPX4 expression was positively correlated with the expression levels of monocyte markers (CD14 and CD115) and M2 macrophage markers (VSIG4 and MS4A4A) both in ESCA and in head and neck squamous cell carcinoma (HNSC). In summary, SLC7A11, GPX4, and AIFM2 are dysregulated in many types of cancers, and are candidate prognostic biomarkers for many types of cancers, and can be used to evaluate the infiltration of immune cells in tumor tissues.

Esophageal Cancer Stem-like Cells Resist Ferroptosis-Induced Cell Death by Active Hsp27-GPX4 Pathway

“…We further demonstrated that the expression of GPX4 in tumorous specimens from esophageal cancer patients is correlated with a poor prognosis ( Figure 5 A,B). Our findings also support recent studies that identified ferroptosis-related gene signatures, which can be used to predict the prognosis and immunological responses of esophageal squamous cell carcinoma and other cancers [ 30 , 31 ].…”

Ferroptosis: A New Strategy for Cancer Therapy

“…Firstly, several studies have shown that inhibiting the expression of GPX4 gene can effectively kill tumor cells through ferroptosis. Furthermore, GPX4 is a candidate prognostic biomarker for many cancers ( 74 ), so it is necessary to further clarify whether GPX4 is an oncogene. Secondly, immunotherapy is a relatively new anti-tumor treatment, and its relationship with ferroptosis is in the preliminary exploration stage.…”

The Role of Cystine/Glutamate Antiporter SLC7A11/xCT in the Pathophysiology of Cancer

“…Analysis of 21 different types of cancer in 7462 cancer samples showed that both SLC7A11 and GPX4 are overexpressed in colorectal cancer (CRC) ( 121 ). Elesclomol, a copper chelator, suppresses CRC both in vitro and in vivo by inducing ROS accumulation and is associated with downregulation of SLC7A11 protein levels via ubiquitination and degradation ( 122 ).…”