Identification of key ferroptosis genes and subtypes in kidney renal clear cell carcinoma.

ABSTRACT

Tumour immunity is highly important for the occurrence and development of tumours, and many cancers are resistant to ferroptosis. This study aims to explore the relationship between ferroptosis-related genes (FRGs) and the immunological characteristics of kidney renal clear cell carcinoma (KIRC). We obtained RNA-seq profiles and clinical data of KIRC patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and identified CD44 and GLRX5 as the key FRGs involved in KIRC immune infiltration through Spearman's correlation analysis. Based on the expression of CD44 and GLRX5, the consensus clustering algorithm was used to classify the TCGA-KIRC samples into two clusters. A nomogram was constructed to evaluate the prognosis of KIRC patients. ESTIMATE, CIBERSORT, and single-sample gene set enrichment analysis (ssGSEA) were performed to evaluate immune infiltration between the two clusters. A weighted gene co-expression network analysis (WGCNA) was used to identify the most relevant genes to the clusters and immunity. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. The external dataset GSE53757 was used to validate the immunological features between the two clusters. Cluster 2 patients had more active immune infiltration and might be more sensitive to immunotherapy; Cluster 2 patients also had a worse prognosis and might be at a more advanced stage of KIRC. We identified key ferroptosis-related genes and subgroups involved in the immune infiltration of KIRC, which is highly important for exploring the molecular mechanisms and treatments of KIRC.