Ferroptosis Patterns Correlate with Immune Microenvironment Characterization in Gastric Cancer

Abstract

Objective:We aimed to build a ferroptosis-based classifier to characterize the molecular features of gastric cancers (GC) and investigate the relationship between different ferroptosis patterns and GC tumor microenvironment (TME). Methods: Based on the genomic and clinical information from TCGA portal and GEO database, non-negative matrix factorization (NMF) was used to identify ferroptosis subtypes in GC patients. In order to estimate the ferroptosis levels, we established ferroptosis subtype score (FSS) to quantify ferroptosis patterns and ferroptosis potential index (FPI) by principal component analysis (PCA). The correlations of different ferroptosis patterns with TME cell-infiltrating characteristics (including immune cell infiltration, immune checkpoints expression levels, tumor mutational burden (TMB) and immunotherapy response) were systematically analyzed. Results: Two ferroptosis subtypes, C1 (with lower FSS) and C2 (with higher FSS), were determined. C2 displayed a significantly lower FPI than C1. Besides, C2 was associated with diffuse subtype while C1 with intestinal subtype. As for TME characteristics, C2 was in accordance with the immune-excluded phenotype as it showed more active immune and stromal activities but lower TMB, less probability of immunotherapy response and poorer prognosis. C1 was linked to immune-inflamed phenotype as it had lower stromal activities but increased neoantigen load, enhanced response to immunotherapy and relatively better prognosis. Conclusion:The systematic assessment of ferroptosis patterns and ferroptosis levels presented in our study implied that ferroptosis serves as an important factor in the formation of TME, which may expand the understanding of TME and provide a novel perspective for the development of targeted immunotherapeutic strategies for GC patients.

Identification of lncRNA-mRNA network linking ferroptosis and immune infiltration to colon adenocarcinoma suppression

“…In addition, a recent systematic review and meta-analysis demonstrated that promoting ferroptosis significantly benefits cancer prognosis [ 41 ]. Moreover, we observed a positive correlation between FS and IS in the COAD samples, a similar trend was also observed in other cancer types, such as gastric cancer [ 42 ]. Since the correlation between various immune cells in the TIME and ferroptosis of colon cancer cells is not well understood, we estimated the infiltration levels of immune cells in the tumor microenvironment of each sample.…”

Loss of GABARAPL1 confers ferroptosis resistance to cancer stem‐like cells in hepatocellular carcinoma

“…In the past year, dozens of bioinformatics articles investigated the correlation of FRG in cancers [23][24][25] For instance, Liang et al constructed a 10-FRG RS model that effectively predicted HCC patient prognosis in both discovery and validation cohorts, and showed that high-risk patients had attenuated antitumor immunity [23]. In this article, the difference was that we focused on FRSG, a set of genes related to ferroptosis as well as stemness.…”

Role of ferroptosis and ferroptosis-related non-coding RNAs in the occurrence and development of gastric cancer

“…Ferroptosis-related genes NOX4, CHAC1, and HIF1A were the prognostic biomarkers of gastric adenocarcinoma ( Xiao et al, 2022 ). In addition, it was also found that the ferroptosis pattern in GC is related to the characteristics of immune microenvironment ( Jiang X. et al, 2021 ; Liu S. J. et al, 2021 ; Wang F. et al, 2021 ). The establishment of markers associated with ferroptosis will help to predict the biological characteristics of GC and select the appropriate treatment for GC patients.…”