Figure 4 from Loss of STK11 Suppresses Lipid Metabolism and Attenuates KRAS-Induced Immunogenicity in Patients with Non–Small Cell Lung Cancer

Mutant KRAS-induced immunogenicity is associated with increased lipid metabolism. A, Tissue biopsies from treatment-naïve patients with NSCLC were subjected to whole-transcriptome RNA-seq. Patients were grouped based on KRAS and TP53 mutation statuses and gene set enrichment analysis (GSEA) performed. Significantly altered gene sets involved in tumor immunity, apoptosis, or metabolism are shown using a Z-score cutoff of 2.5. Focused heatmaps are shown for select, significantly altered genes in the (B) adaptive immune response gene set or (C) glycerophospholipid metabolic process gene sets, both using a FDR-adjusted P value of <0.05. D, Patients were grouped based on KRAS and STK11 mutation statuses, and GSEA performed as previously and significantly altered gene sets involved in the adaptive immune response shown. Focused heatmaps are shown for select, significantly altered genes in the (E) lymphocyte-mediated immunity gene set or (F) cell activation involved in immune response gene sets, both using a FDR-adjusted P value of <0.05. Patients were again grouped based on KRAS and STK11 mutation statuses and GSEA performed. Significantly altered gene sets are shown for pathways involved in G innate or humoral immunity, (H) apoptosis/cell death, or (I) lipid metabolic processes. Focused heatmaps are shown for select, significantly altered genes in the (J) glycerolipid biosynthetic process gene set or (K) glycerophospholipid metabolic process gene set, both using a FDR-adjusted P value of <0.05.