Assessment of structural and functional characteristics of HDL and LDL in lung cancer patients in order to elucidate mechanisms of cholesterol metabolic pathways disorders

Abstract

Introduction: Cholesterol metabolism dysregulation is recognized as one of the hallmarks of the cancer with highest mortality rate and the second most common malignancy – lung cancer (LC). LDL and HDL particles, the latter being carriers of the antioxidant paraoxonase-1 (PON1), were already proven to be altered in cancer pa- tients. We have tried to investigate in more depth the cholesterol metabolism perturbances in LC, by analzying content of each of the LDL and HDL subclass and (anti)oxidative activity of each of the HDL subclass separately. Materials and Methods: LDL and HDL subclasses from blood samples of 89 LC patients and 84 healthy subjects were separated and HDL subclasses PON1 activity assessed using Rainwater method and Gugliucci’s zymogram method, respectively. Results: LC patients had higher relative proportion of HDL 2 particles, lower proportion of HDL 3 particles, and significantly lower activity of PON1 compared to control group (CG). Relative proportion of PON1 activity was higher on HDL 2b fraction and lower on all HDL 3 fractions of LC patients compared to CG. Relative proportions of LDL I and LDL II particles were increased, while proportions of LDL IV and small dense LDL particles were decreased in LC patients. Relative proportions of HDL and LDL subfractions and PON1 activities on HDL sub- fractions were found to be dependent on LC type and size, number of comorbidities and sites of progression, and overall response to therapy. Conclusion: PON1 activity and lipoprotein subfractions distribution seem to be indicators of possible metabolic pathways (disorders) in L