Fig. 2: LKB1 regulates ICAM1 expression in non-small cell lung cancer. | Nature Communications

Fig. 2: LKB1 regulates ICAM1 expression in non-small cell lung cancer.

From: CDK4/6 inhibition triggers ICAM1-driven immune response and sensitizes LKB1 mutant lung cancer to immunotherapy

Fig. 2

a Enrichment analysis on DEGs in the cancer cells between KL (n = 701 cells) versus K (n = 662 cells) using clusterProfiler for gene sets in GO terms. b Venn diagram showing the overlap of DEGs between LKB1 wild-type and mutated groups both in tissues (GSE72094, n = 374 for LKB1-WT, n = 68 for LKB1-MUT) and cells (A549 cells, n = 3 for LKB1-WT, n = 3 for LKB1-MUT). Overrepresentation analysis was performed using these overlap genes, and the top 20 immune-specific signatures were revealed. Ranking of the genes among these enriched signatures according to their frequency. c Plot displays ICAM1 expression level in lung adenocarcinoma patient samples with (n = 73) and without (n = 437) LKB1 mutation. d Representative images and corresponding quantification of IHC staining of ICAM1 in human LUAD tumor sections in LKB1 wild-type and mutated groups. Scale bar, 50 μm (40×). n = 11 (WT) or n = 7 (MUT) biologically independent samples examined over 1 independent experiment. **p = 0.0128. e Relative RPKM values of ICAM1 in LKB1 mutant versus LKB1 wild-type lung cancer cells from CCLE, with or without KRAS co-mutations. Mutant KRAS: n = 7 with mutant LKB1, n = 14 with WT LKB1. WT KRAS: n = 10 with mutant LKB1, n = 38 with WT LKB1. Middle line: median; box edges: 25th and 75th percentiles; whiskers: the upper and lower ends of the whiskers signify the maxima and minima, respectively. Most extreme points that do not exceed ± interquartile range × 1.5; further outliers are marked individually. **p = 0.0066, **p = 0.0011. f Immunoblot (IB) of the indicated proteins in lung cancer cells with LKB1-loss or LKB1-intact. n = 3 experiments. g, h A549 and H460 lung cancer cells were transfected with lentivirus expressing the indicated genes (Ctrl, LKB1-WT, and LKB1-Mut). ICAM1 expression was analyzed by immunoblot (g, n = 3 experiments.) and flow cytometry (h; left, representative images; right, quantification of results. n = 3 biologically independent samples examined over 1 independent experiment. ****p < 0.0001, ****p < 0.0001.) (Results are presented as mean ± SEM. One-way ANOVA followed by Tukey’s multiple comparisons test, two-tailed Student’s t-test or two-tailed Fisher’s exact test was used to analyze the data. **p < 0.01; ***p < 0.001; ****p < 0.0001. Source data are provided as a Source Data file.).

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