Extended Data Fig. 5: In vitro validation of PKAA-EGFR synthetic lethal interaction.
(a) A Kaplan-Meier plot showing distinct survival probabilities of bladder cancer patients with both low PKAA and EGFR protein levels. The p-value is based on a log-rank test. Shaded areas denote the 95% confidence intervals. N represents the number of patients in each group (both low: N = 77; and others: N = 257). (b) A forest plot of hazard ratios for PKAA protein and clinical variables. The p-values are based on a multivariate Cox proportional hazards model. The center point of each horizontal bar represents the estimated hazard ratio. N represents the number of patients. (c) Box plots showing the differential gene dependency of PKAA between samples with EGFR deletion (N = 125) and amplification (N = 463). The middle line in the box is the median, the bottom and top of the box are the first and third quartiles, and the whiskers extend to the 1.5× interquartile range of the lower and the upper quartiles, respectively. N represents the number of cell line samples. (d) Enrichment of EGFR inhibitors in drugs resistant to high PKAA levels. The p-value is based on Fisher’s exact test. (e, f) Relative mRNA level of PKAA in PKAA-KD A549 or H226 cells. N = 2 independent replicates were examined for each condition. (g-l) Drug response assays at 72 h for A549 (g-i) or H226 (j-l) PKAA-KD and control cells treated with three EGFR inhibitors, Afatinib, Erlotinib, and Osimertinib (DMSO and 9 drug concentrations). N = 3 independent replicates were examined for each treatment and perturbation. Data are shown as mean ± SEM. The p-values are based on ANOVA.
