Yixin Yin

Patients with advanced-stage or treatment-resistant colorectal cancer (CRC) benefit less from traditional therapies; hence, new therapeutic strategies may help improve the treatment response and prognosis of these patients. Ferroptosis is an iron-dependent type of regulated cell death characterized by the accumulation of lipid reactive oxygen species (ROS), distinct from other types of regulated cell death. CRC cells, especially those with drug-resistant properties, are characterized by high iron levels and ROS. This indicates that the induction of ferroptosis in these cells may become a new therapeutic approach for CRC, particularly for eradicating CRC resistant to traditional therapies. Recent studies have demonstrated the mechanisms and pathways that trigger or inhibit ferroptosis in CRC, and many regulatory molecules and pathways have been identified. Here, we review the current research progress on the mechanism of ferroptosis, new molecules that mediate ferroptosis, including coding and non-coding RNA; novel inducers and inhibitors of ferroptosis, which are mainly small-molecule compounds; and newly designed nanoparticles that increase the sensitivity of cells to ferroptosis. Finally, the gene signatures and clusters that have predictive value on CRC are summarized.

Aberrant expression of genes contributes to the chemoresistance of colorectal cancer (CRC) treatment. This study aimed to identify genes associated with the chemoresistance of oxaliplatin-based chemotherapy in CRC patients and to construct a signature. Oxaliplatin resistance-related genes were screened by analyzing the gene profiles of cell lines and tissue samples that underwent oxaliplatin-based treatment. Oxaliplatin resistance-related genes were used to establish a signature. The association of the signature had clinical significance, so the prognostic value of the signature was analyzed. Independent cohorts and CRC cell lines were used to validate the value of the gene signature and the oxaliplatin-resistant genes. There were 64 oxaliplatin resistance-related genes identified after overlapping the genes from the dataset of oxaliplatin-treated CRC cells and the dataset of patients treated with oxaliplatin-based chemotherapy. A gene signature based on five oxaliplatin resistance-related genes was established. This gene signature effectively predicted the prognosis of CRC patients who underwent chemotherapy. No significant associations were found between the gene mutations and survival of the patients; however, two genes were associated with microsatellite instability status. Two external independent cohorts and CRC cell line experiments validated the prognostic values of the signature and expression of the genes after oxaliplatin treatment. In conclusion, the oxaliplatin resistance-related gene signature involving five genes was a novel biomarker for the prediction of the chemotherapy response and prognosis of CRC patients who underwent oxaliplatin-based chemotherapy.