Immunological profiling of ferroptosis genes in cetuximab-resistant colorectal cancer and predictive analysis via traditional Chinese medicine

Objective To investigate iron death genes associated with cetuximab resistance in colorectal cancer and their underlying mechanisms, immune profiles, and targeted herbs.Methods The database was used to screen iron death genes, explore their functions and pathways, construct PPI networks, validate the expression and screen the core genes, analyze the mutations and immune infiltration, explore the relevance of immune modulators, and predict the targeted traditional Chinese medicines.Results 122 iron death genes associated with cetuximab resistance in colorectal cancer were obtained, which were mainly involved in biological processes such as immune response, cell proliferation and transcriptional regulation, and involved in signaling pathways such as hepatitis B and cancer. Constructing the PPI network, we found that the expression of TP53, SOX2 and NOS2 was significantly abnormal in colorectal cancer tissues, which was significantly correlated with patient prognosis. All three genes were mutated to varying degrees in colorectal cancer samples and were significantly associated with a variety of immune cells and immunomodulators. Ten targeted Chinese medicines, including ginseng leaves and ginseng, were predicted to potentially intervene in the iron death gene action on cetuximab resistance in colorectal cancer.Conclusion Iron death genes TP53, SOX2 and NOS2 are associated with cetuximab resistance in colorectal cancer, and ginseng leaves and ginseng, as potential targeting traditional Chinese medicines, provide an important theoretical basis for the study of the resistance mechanism of cetuximab and treatment of colorectal cancer.