Radiotherapy Treatment Effects on the Energy Metabolism in LUNG, Head and Neck Cancer Patients

Abstract

Radiotherapy (RT) treatment can produce metabolic changes in cancer patients. The application of metabolomics to the study of energy metabolism in cancer is an underdeveloped issue, and only a few studies have investigated this in lung (LC) and head and neck cancer (HNC) patients exposed to RT, despite its potential relevance in clinical practice. The aims of our study were to analyze the changes produced by RT on the activity and concentration of serum PON1 and the variations in the lipoprotein profile and energy metabolites in LC and HNC patients and to correlate these changes with the clinical and pathological characteristics of patients and tumors, and their response to treatment. The study included LC patients (n=33) and HNC patients (n=28) treated with RT. Control group (n= 50) was formed by Mediterranean health people. Blood samples for analyses were obtained before and after the irradiation procedure. Lipoprotein profile and energy metabolites carried out by nuclear magnetic resonance and gas chromatography-mass spectrometry. Statistical analysis was performed with a statistical analysis software. Relative to control, both cancer groups had significantly lower serum PON1 concentration, and arylesterase activity (p<0.001). However, after RT increased PON1 concentration in cancer patients but also arylesterase activity decreased. This low activity was correlated with an increase of pulmonary toxicity. Intermediate density lipoprotein (IDL), triglycerides linked with different lipoprotein profiles and the VLDL particles size were significantly higher in cancer groups in comparison to control group. Whereas leucine, isoleucine, valine, 3-hydroxybutyrate, and serine metabolites were significantly lower in cancer groups, succinate, malate, aspartate, pyruvate, glutamine and glutamate were significantly higher in the same groups. LC and HNC patients showed significantly differences in leucine, isoleucine, serine, aconitate and citrate metabolites between before and after RT treatment. Our study demonstrates that RT treatment can modulate anti-oxidant defense mechanisms and metabolites related to one carbon metabolism in cancer patients. These results could be useful as a biomarker to predict RT response and the prognosis of patients.