Active oxidative metabolism and impaired glyoxalase system amid elevated intracellular oxidative stress in non-small cell lung cancer shown by immediate post surgery alkylation and redox proteomics

Reactive oxygen species can oxidatively modify enzymes to reroute metabolic pathways according to tumor needs but we lack overview of all potential targets. Thiol groups are most susceptible to oxidative modifications but rarely analyzed in clinical settings due to their reactivity.

To accurately address the cross-talk between redox signaling and metabolism we collected tumor and healthy tissue from 70 individuals with non-small cell lung cancer right after surgery into a thiol-quenching solution, then carried out redox-proteomics based on relative MS1 quantitation of isotope labeled cysteines discriminating between their reductive and oxidative state and averaging redox ratios of different peptides for the same site.

As a result of such an unbiased and meticulous approach, we, for the first time, show evidence of higher oxidation of a number of key metabolic and especially glucose related enzymes and their specific cysteine sites in tumor. Integrating redox and standard label free quantitative proteomics we demonstrate that lung cancer strives to maintain oxidative metabolism amid the rise of intracellular oxidative stress. We also report both redox and protein level deactivation of the glyoxalase system, which might be compensated by higher excretion or lower production of toxic methylglyoxal, aiding cancer progression.