Fig. 1

MSI2 expression is increased in CRC and positively correlated with the expression of ferroptosis-related inhibitory molecules. A The expression of MSI2 is upregulated in the CRC TCGA database from GEPIA (COAD, N = 349, T = 275; READ, N = 318, T = 92). B MSI2 mRNA expression was measured by qRT‒PCR in 50 paired clinical CRC specimens. C MSI2 protein expression was increased in colon primary tumors from CPTAC (N = 100, T = 97). D Representative IFC images of MSI2 expression in our clinical CRC specimens. Blue: DAPI, green: MSI2; Scale bars, 200 μm. E Heatmap of ferroptosis-related gene expression in MSI2-high (n = 310) and MSI2-low (n = 310) patients from TCGA CRC datasets and in normal tissues (n = 779) from GTEx. The different colors represent the expression trend of the indicated gene in different samples. F The volcano plot of the differentially expressed ferroptosis-related genes in MSI2-high (n = 310) and MSI2-low (n = 310) patients, “Adjusted p < 0.05 and Log2(Fold Change MSI2-high/MSI2-low) > 1.3 or < − 1.3” were defined as the threshold for DEGs. G The top up-regulated and down-regulated KEGG pathway enriched by the differentially expressed genes in MSI2-high (n = 310) and MSI2-low (n = 310) patients. H The mRNA expression distribution of ferroptosis-related inhibitory molecules in MSI2-high (n = 310) and MSI2-low (n = 310) patients. The abscissa represents differentially expressed ferroptosis-related inhibitory genes, and the ordinate represents the expression distribution of genes. I The positive correlations between MSI2 and ferroptosis-related inhibitory genes were analyzed by Spearman correlation analysis in the TCGA CRC datasets, n = 620. J Heatmap of positive correlations between MSI2 and ferroptosis-related inhibitory genes were analyzed by Spearman correlation analysis and normalized by GAPDH in the GEPIA COAD and READ database, n = 367. K The positive correlations between MSI2 and ferroptosis-related inhibitory genes were analyzed by Spearman correlation analysis in the TIMER COAD database, n = 457. The ferroptosis-related genes set (H-K) were obtained from the public available FerrDb databases (http://www.zhounan.org/ferrdb/current/). L Representative images of necrotic cell death and TUNEL staining in MSI2-high and MSI2-low clinical CRC adenocarcinoma tissues. Blue: DAPI, red: MSI2, green: TUNEL; H&E, Scale bars, 200 μm (left) and 50 μm (right); IFC, Scale bars, 200 μm and 100 μm. and statistical analysis of TUNEL-positive cell percentages from MSI2-high and MSI2-low adenocarcinoma tissues. These results are presented as the mean ± SD values; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; B paired 2-tailed Student’s t test, A, C, H Wilcox test, E Kruskal‒Wallis test, I-K Spearman correlation analysis and L unpaired 2-tailed Student’s t test