Comprehensive Analysis of Ferroptosis‐Related Markers for the Clinical and Biological Value in Gastric Cancer

Abstract

Gastric cancer is a highly malignant tumor with poor survival rate. Ferroptosis, a newly defined regulated cell death, is closely related to several tumors. Introduction of ferroptosis is promising for cancer treatments. However, the predictive role of ferroptosis in GC remains elusive. In this study, we screened the ferroptosis-related genes which were differentially expressed between normal and GC tissues. Then, based on these differentially expressed genes (DEGs), the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions were applied to construct the 10-gene prognostic signature (SP1, MYB, ALDH3A2, KEAP1, AIFM2, ITGB4, TGFBR1, MAP1LC3B, NOX4, and ZFP36) in TCGA training dataset. Based on the median risk score, all GC patients in TCGA training dataset and GSE84437 testing dataset were classified into a high- or low-risk group. GC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group ( P < 0.001 ). Combined with the clinical characteristics, the risk score was proven as an independent factor for predicting the OS of GC patients. Besides, the GC patients in the high- or low-risk group showed significantly different GO and KEGG functional enrichments, somatic mutation, fractions of immune cells, and immunotherapy response. Then, the expression levels of these genes in signature were further verified in the GC cell lines and our own GC samples (30-paired tumor/normal tissues). Furthermore, the effects of ferroptosis inducer Erastin on these 10 ferroptosis-related genes in GC cell lines were also explored in our study. In conclusion, our study constructed a prognostic signature of 10 ferroptosis-related genes, which could well predict the prognosis and immunotherapy for GC patients.

Prediction of Prognosis in Patients With Endometrial Carcinoma and Immune Microenvironment Estimation Based on Ferroptosis-Related Genes

“…Similarly, several studies have shown that AIFM2 represents an unfavorable prognostic factor in prostate cancer, acute myeloid leukemia and uveal melanoma (Luo and Ma, 2021;Lv et al, 2021;Song et al, 2021). However, a recent study has indicated that AIFM2 act as a favorable factor for OS of gastric cancer patients, which is consistent with the findings of our study (Shao et al, 2021). Therefore, it is interesting to explore the effect of AIFM2 on the prognosis of different types of tumors.…”

Establishment of an endoplasmic reticulum stress-related signature predicting outcomes of gastric adenocarcinoma patients

“…Unexpectedly, low-risk GAC patients had a greater TMB, suggesting that low-risk patients may be more likely to benefit from immunotherapy. This result is consistent with the findings of Shao et al (2021 ). Among the common ICPs, however, only the expression of PDL2 was significantly higher in the high-risk group.…”

Ferroptosis and its Role in Gastric Cancer

“…Consistent with the studies on the relationship of iron and GC, ferroptosis has also been found to be closely related to the proliferation, invasion, and metastasis in GC ( Chen et al, 2021a ; Huang et al, 2021 ). However, the predictive role of ferroptosis in GC remains elusive ( Shao et al, 2021 ). Thus, understanding the processes underlying ferroptosis is promising for the development of cancer treatment strategies.…”

“…Biomarkers for the characterization of the tumor immune microenvironment may add to the predictive value of the current staging system ( Jiang et al, 2019 ). In recent decades, large-scale clinical trans-omics studies allowed the identification of some crucial ferroptosis-related genes as reliable biomarkers to describe the tumor immune microenvironment landscape and predict response to antitumor therapy ( Liu S. J. et al, 2021 ; Shao et al, 2021 ).…”