Abstract

Introduction: Colorectal cancer (CRC) is a common malignant tumor with high incidence and poor prognosis. Identifying effective biomarkers is crucial for its diagnosis and treatment.Methods: Gene expression data were obtained from TCGA-CRC and GSE39582 datasets. After preprocessing, differentially expressed genes (DEGs) were screened using the limma package. Hub genes were identified via WGCNA, miRNA-hub/TF-hub gene network construction, and LASSO, SVM-RFE, and random forest algorithms. Subtype analysis, survival analysis, external validation, qRT-PCR, Western blot, and ferroptosis-related assays were performed.Results: Fourteen ferroptosis-mitochondria-RBP-related genes (IMRBPs) were identified, including seven hub RBP genes (APEX1, BRCA1, DNMT1, EZH2, PTTG1, SND1, UHRF1). APEX1 was downregulated in CRC, while the other six were upregulated. The diagnostic model based on these seven genes showed high AUC values (0.818-0.924) in multiple datasets. These hub genes were associated with ferroptosis suppression by regulating GSH/GSSGand Fe²⁺ levels.Discussion: The seven hub RBP genes are potential biomarkers for CRC, providing new insights and therapeutic targets. However, functional validation and larger sample sizes are needed for clinical application.