Fig. 3: Transcriptome analysis revealed that MYC is the key regulator of the antitumor effects of anlotinib combined with KRAS-G12Ci.

A Enriched hallmark pathways of primary resistant cell lines (Calu-1, SW1573, H23) compared with sensitive cell lines (H358, H2122, H2030). Normalized enrichment score (NES) is plotted. False discovery rate (FDR) < 0.25 is marked in red. Data are from CCLE datasets. B Volcano plot showing the transcriptional difference of H2122SR compared with H2122 parental cell line. Genes with log₂FC > 2 and adjusted p value < 0.05 were marked in red. Genes with log₂FC < −2 and adjusted p value < 0.05 were marked in blue. C Enriched hallmark pathways of H2122SR compared with H2122 parental cell line. Normalized enrichment score (NES) is plotted. FDR < 0.25 is marked in red. FDR > 0.25 is marked in blue. D Enriched hallmark pathways of H2122SR treated with anlotinib (2 μM) plus sotorasib (1 μM) for 24 h compared with vehicle. Normalized enrichment score (NES) is plotted. FDR < 0.25 is marked in red. Combo: anlotinib plus sotorasib. E GSEA enrichment plot of MYC targets V1 pathway of H2122SR treated with anlotinib (2 μM) plus sotorasib (1 μM) for 24 h compared with vehicle. F Barplot comparing NSE and FDR of MYC targets V1 and MYC targets V2 pathways enriched in different treatment groups: DMSO, anlotinib (2 μM), sotorasib (1 μM), and combo (anlotinib plus sotorasib) for 24 h. FDR < 0.25 is marked in red. FDR > 0.25 is marked in blue. Combo: anlotinib plus sotorasib.