Abstract
Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. Increasing evidence has shown that ferroptosis plays a significant regulatory role in the occurrence and progression of cancer. However, new biomarkers associated with ferroptosis and new ferroptosis-related subtypes in CRC remain to be identified. We collected a colon adenocarcinoma (COAD) dataset from the cancer genome atlas (TCGA) database in UCSC Xena. Ferroptosis-related genes (FRGs) were extracted from the dataset, and we conducted gene expression profiling interactive analysis (GEPIA), cBioPortal analysis, and immune cell infiltration analysis. Additionally, we used the "ConsensusClusterPlus" R package to identify ferroptosis-related subtypes of CRC. Based on these subtypes, we analyzed their prognostic features, gene co-expression networks, and the ferroptosis landscape. We identified 21 FRGs in COAD. The genes RBMS1, NOX4, FABP4, CYB5R1, CPEB1, and ATM were significantly and positively correlated with immune cell infiltration and poor prognosis. Furthermore, we identified two COAD subtypes related to prognosis and ferroptosis (ferroptosis subtype 1 [FS1] and ferroptosis subtype 2 [FS2]). These subtypes were associated with tumor mutation burden (TMB), mutation status, immunogenic cell death (ICD), and immune checkpoint (ICP) regulatory genes. Finally, we established a ferroptosis landscape of COAD. We identified key ferroptosis-related genes and defined two distinct ferroptosis-associated subtypes in CRC that differ significantly in prognosis and immune infiltration. These findings provide new insights into the interaction between ferroptosis and the tumor immune microenvironment, offering potential biomarkers and therapeutic targets for improved diagnosis and personalized treatment of colorectal cancer.