Fig. 1
CDC7 is upregulated during NE transformation in lung and prostate tumors. a Schematic of the generation of a PDX-derived, short-term cultured cell line generation, derived from the T-SCLC PDX Lx_151, and handling for the performance of CRISPR-Cas9 KO screen to identify therapeutic vulnerabilities of T-SCLC. Created with BioRender.com. b Plot showing genes for which sgRNAs were depleted in the CRISPR-Cas9 KO screen, ranked by p-value. Red dots are indicative of genes passing the p-value threshold. CDC7 mRNA expression c and protein abundance (d) in lung cancer clinical specimens, categorized as control never transformed adenocarcinomas (LUAD, RNA n = 11, protein n = 46), transforming adenocarcinomas (T-LUAD, RNA n = 11, protein n = 10) and small cell carcinomas (T-SCLC, RNA n = 11, protein n = 20) and control de novo small cell carcinomas (SCLC, RNA n = 16, protein n = 50). For (d), H-score medians and standard deviations (right) and representative immunohistochemistry (IHC) images (left) are shown. (e) CDC7 mRNA expression in prostate adenocarcinoma (PRAD) tumors with (n = 22) or without (n = 210) NE features (data from.22 (f) CDC7 protein expression in PRAD (n = 30) and NEPC (n = 7) PDX, as assessed by IHC. H-score medians and standard deviation (right) and representative images (left) are shown. p-value legend: *<0.05, **<0.01, ***<0.001
