Fig. 6: FA analysis reveals the excess of palmitate and its monounsaturated metabolites in the tumors of the aggressive LUAD phenotype.

a Relative comparison of selected free fatty acid levels obtained through a full scan untargeted LC-HRMS profiling. FA annotation was done by the accurate mass and retention time (AMRT) matching against standard database. No MS/MS spectra are available due to well-known low fragmentation efficiency of FAs in negative ionization mode. Barplots with data points are levels of annotated FA in LUAD tumors of long– and short-survival patients and represent mean values +/− S.E.M. Two-sided p-value < 0.05 considered significant and corresponds to a Student’s t-test (n = 5 samples per LUAD T subtype). b Protein expressions of Stearoyl-CoA Desaturase (SCD1), (n = 7 biological replicates per group). GAPDH is used as loading control. Boxplot represents mean ± S.E.M expressed as arbitrary units normalized to the mean of long-term survival subtype. The p-value from two-sided Student’s t-test. c–f, the absolute tumor concentration of the FAs of interest, hexadecenoic/palmitic, palmitoleic, oleic and eicosapentaenoic acids, respectively, determined through the internal standard spike using isotopically labeled standards and multipoint calibration curves. The p-value corresponds to two-sided Wilcoxon signed rank test (n = 5 biological samples per LUAD subtype). g Schematic of proposed lipid remodeling in aggressive LUAD. dd-ABPP analysis revealed increased catalytic fractions of serine lipases interacting with palmitoylated lipoproteins in aggressive tumors. Increased lipase activities degrade substrate lipoproteins into naked proteins and palmitoyl residues, triggering lipid composition remodeling in aggressive tumors. PPIs correspond to protein-protein interactions. Data in (a), (c–f) are presented as mean values +/− SEM. Source data are provided as a Source Data file.