Systemic redox status in lung cancer patients is related to altered glucose metabolism

Abstract

Altered systemic redox status is often observed in lung cancer. However, detailed information on factors other, than smoking, which influence this perturbation is rather scarce. Elevated oxidative stress has been linked with disturbances in glucose metabolism before, but such associations have not been investigated in lung cancer. The aim of this study was to evaluate the relationship between systemic parameters of glucose metabolism and redox status in lung cancer patients (LC). Biochemical variables related to circulating glucose, i.e. glucose, insulin, c-peptide, fructosamine (FA), and glucose metabolism, i.e. β-hydroxybutyrate (BHB), lactate (LACT), non-esterified fatty acids (NEFAs), as well as redox status i.e. total antioxidant status (TAS) and total oxidant status (TOS) were determined for LC (n = 122) and control subjects (CS) (n = 84). HOMA-IR and the oxidative stress index (OSI) were calculated. LC patients had an altered redox status and glucose metabolism compared to CS. Positive correlations in LC were observed between TOS, OSI and circulating glucose as well as FA, while TAS positively correlated with BHB and NEFAs. In contrast, in metastatic LC, NEFAs and BHB positively correlated with OSI. Smoking status additionally stratified the observed relationships. In conclusion, we found that parameters related to circulating glucose or non-enzymatic glycation were correlated with oxidative stress (TOS and OSI), while metabolites such as BHB and NEFAs were correlated with antioxidant capacity (TAS). Metastasis prevalence and smoking seem to influence these correlations. However, the detailed mechanism of this relationship requires further research, in particular as regards the surprising positive correlation between NEFAs and TAS.

A High-Performing Plasma Metabolite Panel for Early-Stage Lung Cancer Detection

“…Elevated plasma levels of β-hydroxybutyric acid, one of the most abundant plasma ketone bodies, was found for NSCLC at all stages. Consistent with our results, several other recently published studies have detected the same trend in plasma β-hydroxybutyric acid from lung cancer patients [47][48][49]. The biological functions of β-hydroxybutyric acid are quite diverse and include energy metabolism, epigenetic regulation, and oxidative stress response [50].…”

Transcriptome analysis reveals gender-specific differences in overall metabolic response of male and female patients in lung adenocarcinoma

“…Furthermore, systemic oxidative stress is associated with the pathogenesis of lung cancer and many other site-specific cancers. Clinical research suggests circulating glucose or non-enzymatic glycation are correlated with oxidative stress, whereas metabolites such as β-hydroxybutyrate and nonesterified fatty acids are linked to total antioxidant status in lung cancer patients [28]. In this study, we found that multiple pathways of amino acid and carbohydrate metabolism were deregulated both in male and female patients.…”

Oxidative stress in lung cancer patients is associated with altered serum markers of lipid metabolism

“…In vitro studies indicated that tumor cells regulate redox balance and counteract oxidative stress triggered by changes in glucose metabolism [20]. However, our previous studies showed that changes in carbohydrate metabolism expressed as alterations in systemic biochemical parameters might also be related to systemic redox alterations [3]. To our best knowledge, at the systemic level such relationships were demonstrated for the first time in oncological disorders.…”

“…Nevertheless, cigarette smoking still remains the main exogenic determinant promoting the generation of reactive oxygen species and thus inducing inflammatory-related airway injuries [2]. Several studies have also indicated that lung cancerogenesis is directly linked with redox imbalance, both in organs and systemic [3,4]. Although the link between cigarette smoking and redox imbalance in lung cancer has been extensively studied and is widely known, factors other than tobacco smoke may contribute to systemic oxidative stress in lung cancer patients, since prevalence of the disease is systematically increasing also among non-smokers [5].…”

“…In our previous studies, we proved that alterations in redox balance in lung cancer may also be influenced by endogenous metabolic disturbances, e.g. alterations in glucose metabolism [3], as well as trace element status disorders [6]. Alterations of lipid metabolism in lung cancer patients have been demonstrated in several cohort and experimental studies and have even been considered as potential risk factors [7–10].…”