Fig. 5: PRSS22 is a key driver of ICT through the modulation of macrophage polarization. | Oncogene

Fig. 5: PRSS22 is a key driver of ICT through the modulation of macrophage polarization.

From: PRSS22 inhibits HMOX1-mediated ferroptosis and induces osteopontin cleavage to promote M2 macrophage polarization and colitis-associated carcinogenesis

Fig. 5: PRSS22 is a key driver of ICT through the modulation of macrophage polarization.

A PRSS22 mRNA expression in intestinal tissue samples from normal individuals (n = 41), non-IBD (n = 50), UC (n = 74), CD (n = 127) and CRC groups (n = 473) in the TCGA and the TaMMa patient cohorts [14, 21]. B Time-course analysis of PRSS22 expression in a CAC mouse model. Data are means ± SD (n = 3). Groups were compared using two-way ANOVA and Dunnett’s multiple comparison tests. C Time-course analysis of PRSS22 expression in an acute DSS-induced colitis mouse model [22]. Data are means ± SD (n = 3). D ssGSEA of transcriptomic data presented in Fig. 3A–F. Data are means ± SD (n = 3). Groups were compared using two-way ANOVA and Sidak’s multiple comparison tests. E–G Analysis of a CRC patient tumour sample single-cell transcriptomic dataset [10]. E UMAP clustering showing differential PRSS22 expression levels at a single-cell level. F M2 macrophage scores in PRSS22-high (n = 88) and low groups (n = 104). G Proportion of SPP1⁺ and other subtypes of macrophages in PRSS22-high (n = 88) and low (n = 104) groups. H, I qPCR analysis of M1 and M2 macrophage markers following the co-culture of THP-1–derived macrophages and HCT116 cells stably expressing shCtrl or shPRSS22. Data represent means ± SD (n = 3). Groups were compared using two-way ANOVA and Sidak’s multiple comparison tests. J Bar plot showing TGFβ expression from transcriptomic data presented in Fig. 3A–F. Data are means ± SD (n = 3). Groups were compared using unpaired t tests. K Intracellular enzyme-linked immunosorbent assay (ELISA) quantification of TGFβ protein levels in HCT116 cells stably expressing shCtrl or shPRSS22. Data are means ± SD (n = 3). Groups were compared using unpaired t tests. In all panels: *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001.

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