Figure 8. GLI2 potentially regulates NKE by non-classic Hedgehog signaling to promote drug tolerance and colorectal immunity escape. (A) Multi-cohort association analysis screens out GLI2 and ODZ4 as the closest genes in regulating NKE. K-M analysis for GLI2 in (B) TCGA cohort and (C) GSE39582 cohort. (D) GLI2 expression between colorectal tissues and adjacent tissues. (E) Correlation analysis between GLI2 and NKE score. (F) Pathways score in ARG subpopulations, and Hedgehog pathway score displays significant differences amongst ARG subpopulations (p < 2.0e-16). (G) The correlation between Hedgehog pathway score and drug scores. (H) Correlation between NKE score and Hedgehog pathway score. (I) NKE-related inflammation factors expression in ARG subpopulations. (J) Correlation between GLI2 and NKE regulators (IL6, TGFβ). (K) Correlation between KNE and NKE regulators (IL6, TGFβ). (L) Pathway network between GLI2 and classic Hedgehog pathway. Gene expression characteristics of non-classic Hedgehog signaling in ARG subgroups in (M) TCGA cohort and (N) GSE39582 cohort.