Comprehensive transcriptomic and metabolomic analyses reveal the link between ferroptosis and gut microbiota in CRC

Abstract Objective Given the high incidence rate and mortality of CRC, we constructed a high-performance early diagnosis model based on ferroptosis-related genes and explored the possible pathway between ferroptosis and intestinal microbiota metabolites. Methods To explore the ferroptosis genes associated with CRC, the gene expression data of GSE14297 was extracted from the GEO database. A series of difference analyses and ferroptosis correlation analyses were carried out. Cytoscape was used to optimize the PPI network, and MCODE was used to screen hub gene modules. 16S rDNA was used to analyze the intestinal flora. MetaboAnalyst 5.0 was used to analyze the correlation between metabolites and genes. Results Compared with normal tissues, 2959 genes were differentially expressed in CRC samples, including 2946 upregulated genes and 13 downregulated genes. 63 overlapping genes were obtained by crossing with ferroptosis genes. Further MCODE analysis showed that 15 hub genes were obtained. The ROC curve showed that the AUC value of NQO1 was 0.929, and the AUC value of the other 14 genes was 1. GO enrichment analysis showed that 15 hub modules were significantly correlated with the functions of "response to oxidative stress", "plasma membrane region" and "antioxidant activity". KEGG pathway analysis showed that ferroptosis, metabolic pathways, and pathways in cancer were enriched. Metabolite pathway analysis showed that in the CRC group, the significantly enriched pathways were neuroactive ligand-receptor interaction, ABC transporters, aminoacyl tRNA biosynthesis, cocaine addition, central carbon metabolism in cancer, information processing, phenylalanine metabolism, and biosynthesis of amino acids. Analysis based on metaboanalyst5.0 showed that 25 differential metabolites were associated with ferroptosis-related genes. Conclusion Based on bioinformatics and 16S rDNA analysis, 25 differential metabolites were found to be associated with ferroptosis-related genes. Ferroptosis-related genes and gut microbes may jointly participate in the progression of CRC.