Fig. 7

MSI2 regulates the TIME in clinical CRC specimens via HMGB1-mediated DC infiltration. A Positive Spearman correlations between MSI2 expression and the abundances of infiltrated immune cell types, including B cells, CD8⁺ T cells, CD4⁺ T cells, macrophages, neutrophils and DCs, in the COAD and READ datasets from TIMER database. B Immune cell score heatmap, different colors represent different MSI2 expression distribution in MSI2-high (n = 310) and MSI2-low (n = 310) CRC patients, the expression distribution of immune score were used immuneeconv-TIMER. C Statistical analysis of TIMER scores of B cells, CD8⁺ T cells, CD4⁺ T cells, macrophages, neutrophils and DCs in MSI2-high (n = 310) and MSI2-low (n = 310) CRC patients. D The percentage abundance of tumor infiltrating immune cells in each CRC specimens from TCGA (n = 620). Different colors indicate the different types of immune cells. E Positive Spearman correlations between MSI2 or (and) HMGB1, CD11b and CD11c expression in GEPIA CRC datasets. F Western blot analysis of MSI2, HMGB1 and K29-HMGB1 expression in 8 paired clinical CRC specimens. G Relative MSI2 and HMGB1 expression in 50 paired clinical CRC specimens. H Pearson correlation coefficients analysis showed a strong positive association between MSI2 and HMGB1 expression in our 50 paired clinical CRC specimens (R = 0.66, p = 1.7e-07). I The protein expression levels of MSI2 and HMGB1 in normal and primary tumor tissues from CPTAC (Normal, n = 100; Primary tumor, n = 97) Colon Cancer dataset. J Positive Pearson correlation between MSI2 and HMGB1 protein expression in the CPTAC Colon Cancer datasets (R = 0.39, p = 9.7e-05). K-L Representative H&E and IHC images of MSI2, HMGB1, CD3, and CD11c staining, histological inflammation score and statistical analysis of the average IHC staining density in MSI2-high and MSI2-low clinical CRC patient tissues. Scale bars, 100 μm. M Lower MSI2 or (and) HMGB1 expression predicted a poorer overall survival prognosis in GEPIA CRC datasets. The cutoff value was set at 50% with normalization to ACTB and analysis by the log-rank test, n = 362. N Nomogram prediction of 1-year, 2-year, 3-year and 5-year overall survival of TCGA CRC patients based on MSI2 expression. The calibration curve for the overall survival nomogram model in each discovery group and the dashed diagonal line represents the ideal nomogram. These results are presented as the mean ± SD values; **p < 0.01, ***p < 0.001, ****p < 0.0001; B-C, I Wilcoxon test, G paired 2-tailed Student’s t test and L Mann–Whitney test