Fig. 1

Identification of EGLN1 as a druggable pro-oncogenic factor in KRAS-driven lung AD. a Schematic representation of the bioinformatics and functional genomics integrative approach. b Cumulative distribution of CERES scores in A549 cells generated with AVANA library (DepMap data) or GeCKOv2 sub-libraries A or B (our screening data). c Comparison between median CERES scores in KRAS mutated (MUT) vs KRAS wild-type (WT) lung cancer cell lines. The genes (n = 1374) with a CERES score significantly different between the two groups (Wilcoxon test pvalue< 0.05) are highlighted in red. The genes (n = 88) with a CERES score significantly different between the two groups (Wilcoxon test pvalue< 0.05) and lower than our dependency threshold (D ≤ − 0.3.) are highlighted in yellow. d Network representation of significant enriched pathways for the 88 essential genes in the KRAS-mutated cell lines. e Comparison of CERES score distributions across the identified druggable targets in KRAS-mutated (MUT) vs KRAS-wild-type (WT) cell lines. f Comparison of CERES scores distributions for the EGLN1 gene in cell lines derived from different tumor tissues. Numbers between brackets on Y axis indicate the number of cell lines considered for each cancer type. g EGLN1 expression in TCGA lung adenocarcinoma patients cohort (N = 572, normal = 59, KRAS WT = 350, KRAS mutated = 154). h EGLN1 expression in a set of surgical samples from our Institute Biobank (N = 9). Cyan dots represent patients carrying a KRAS mutation. i Representative microscopy images of immunohistochemistry staining for EGLN1 expression in lung adenocarcinoma patients. Central image shows the interface between tumor and healthy lung tissue (50x magnification). Higher magnifications (400x) of the healthy lung epithelial tissue (left image) or of the tumor tissue (right image) are provided. Arrows indicate bright positive stained macrophages. The tissue has been counter-stained with hematoxylin. j Kaplan-Meier curve representing overall survival probability in KRAS-mutated patients presenting high (N = 39) or low (N = 39) levels of EGLN1 expression. *p < 0.05; **p < 0.01; ***p < 0.001; ns = not significant