Fig. 7: Dysregulated active enzyme fractions correlate with FDA-identified toxic metals in tobacco smoke and display genetic polymorphism relevant to KRAS-LUAD oncogene.

a Scatter plot represents Spearman rho correlations (rho) of degree of SH catalytic activity with tumor content of nine respective metals. Correlation significance depicts two-sided correlation test p-value < 0.5. (rho> |0.6 | ). b Representative scatter plots with 95% confidence intervals of measured content of endogenous ELANE inhibitors annotated in Merops, with lung tissue concentration of Cr and Al (ng/ml). These metals highly correlated with the proteolytic fraction of ELANE. c Co-occurrence of SHs and KRAS mutations in TCGA KRAS mutated cancers. Barplots show the fraction of patients (%) with the SH mutation that also had mutated KRAS. For each SH gene, we assessed the number of patients with at least one non-synonymous mutation within a gene. Arrow depicts LYPLA2 that displays high co-occurrence of gene mutations with KRAS oncogene and was detected with increased catalytic fractions in aggressive compared with less-aggressive LUAD disease in our study. BH-adjusted Fisher’s test p-value for the co-occurrence of two mutations. SHs detected in the current study and with p-value < 0.01 are shown on the graph. Source data are provided as a Source Data file.