Fig. 1.

ATR and CHK1 are potential therapeutic targets for HCC. a Gene Set Enrichment Analysis (GSEA) indicating that FANCONI pathway and recombinational repair gene sets are enriched in HCC tissues compared with paired non-tumor tissues from the TCGA cohort (n = 50). b Venn diagram showing the overlap of human DNA repair genes (n = 220) and liver cancer essential genes (n = 1021) derived from the Dependency Map database. c Among the 37 overlapping genes, four targetable and ten non-targetable genes were identified, which are upregulated in HCC tissues compared with paired non-tumor tissues from the TCGA cohort (> 2-fold, n = 50). d Schematic representation of the CRISPR-Cas9 based kinome screens performed in MHCC97H cells. MHCC97H cells were infected with a lentiviral kinome gRNA library and cultured for 14 days (T14) in three replicates. gRNA barcodes from T0 and T14 samples were recovered by PCR and analyzed by next generation sequencing. e Representation of the relative abundance of the gRNA barcode sequences from the kinome screens. ATR and CHEK1 were identified as high-confidence lethal genes in MHCC97H cells. The y-axis shows log2-fold change in abundance (ratio of gRNA frequency in T14 sample to that in T0 sample). The x-axis depicts the average read-count in the T0 sample. f Re-analysis of previous kinome screen data in Huh7 and Hep3B cells. ATR and CHEK1 were identified as high-confidence lethal genes in each cell line. g mRNA levels of ATR and CHEK1 in tumor tissues and paired non-tumor tissues in the cohort of TCGA database (n = 50). h Kaplan-Meier curves indicate that high levels of ATR and CHEK1 mRNA correlate with poor prognosis of patients with HCC in the cohort of TCGA database (n = 365). *P < 0.05, **P < 0.01, and ***P < 0.001