摘要：SummaryFerroptosis is a type of programmed cell death potentially playing an important role in colorectal cancer (CRC) development. However, comprehensive investigations toward ferroptosis in human CRC are lacking. Here, we performed multiple investigations on cancer and para-cancer tissues. We demonstrated that the changes of structural variation and chromatin accessibility in CRC were more associated with the altered mRNA expression of ferroptosis-related genes (FRGs), and the expression ofCDKN2A,GPX4,ALOXE3, andLINC00336was related to the overall survival rates. Subsequently, we revealed thatCYBBandYAP1were potentially the hub genes, and thatHSF1andSTAT2were potentially FRGs’ upstream transcription factors. Finally, we depicted the crosstalk between ferroptosis and necrosis, autophagy, and apoptosis. Based on multi-dimensional analyses, we characterized ferroptosis, probable core genes, and the upstream regulators in human CRC. The findings here may improve our understanding of ferroptosis in CRC and provide new opportunities for clinical diagnosis and treatment.Graphical abstractDisplay OmittedHighlights•Characterize ferroptosis in CRC from DNA, RNA, and protein to epigenetic modification•The potentially functional or hub genes in ferroptosis at multiple molecular levels•Putative ferroptosis regulators (transcription factors) in human CRC cells•The genes that probably link ferroptosis to necrosis, autophagy, and apoptosisOncology; Biological sciences; Bioinformatics; Cancer
