NMR-Based Metabolomics in Investigation of the Radiation Induced Changes in Blood Serum of Head and Neck Cancer Patients and Its Correlation with the Tissue Volumes Exposed to the Particulate Doses

Abstract

In the present study, we analyze the nuclear magnetic resonance (NMR) blood serum metabolic profiles of 106 head and neck squamous cell carcinoma (HNSCC) patients during radio (RT) and concurrent radio-chemotherapy (CHRT). Four different fractionation schemes were compared. The blood samples were collected weekly, from the day before the treatment until the last week of CHRT/RT. The NMR spectra were acquired on A Bruker 400 MHz spectrometer at 310 K and analyzed using multivariate methods. Seven metabolites were found significantly to be altered solely by radiotherapy: N-acetyl-glycoprotein (NAG), N-acetylcysteine, glycerol, glycolate and the lipids at 0.9, 1.3 and 3.2 ppm. The NMR results were correlated with the tissue volumes receiving a particular dose of radiation. The influence of the irradiated volume on the metabolic profile is weak and mainly limited to sparse correlations with the inflammatory markers, creatinine and the lymphocyte count in RT and the branched-chain amino-acids in CHRT. This is probably due to the optimal planning and delivery of radiotherapy improving sparing of the surrounding normal tissues and minimizing the differences between the patients (caused by the tumor location and size).

Plasma metabolomics of oral squamous cell carcinomas based on NMR and MS approaches provides biomarker identification and survival prediction

“…Similar NMR results for acetone and threonine were observed by Gupta et al 20 in serum from OSCC cases. In accordance with our data, Boguszewicz et al 42 found increased serum levels of threonine and tyrosine after radiotherapy, which could represent a return to normal concentrations resulting from the treatment. The authors also found increased levels of acetoacetate and acetone and low levels of alanine associated with weight loss in patients treated with radio/chemotherapy, a result that is potentially consistent with our data of decreased BMI in OSCC cases 43 .…”

Uracil as a biomarker for spatial pyrimidine metabolism in the development of gingivobuccal oral squamous cell carcinoma

“…Due to its high reproducibility and capacity for quantitation, NMR has been used successfully to identify cancer biomarkers 25 , 26 . Recently, Boguszewicz et al 27 successfully introduced NMR-based metabolic profiling in patients with head and neck squamous cell carcinoma. Metabolites and metabolic genes have also been identified using other spectroscopy methods applied to investigate radiation-induced changes in such patients.…”

Metabolite Biomarkers of Prolonged and Intensified Pain and Distress in Head and Neck Cancer Patients Undergoing Radio- or Chemoradiotherapy by Means of NMR-Based Metabolomics—A Preliminary Study

“…Three fractionation techniques were used in RT: CONV (conventional fractionation), CAIR (continuous accelerated irradiation) and SIB (accelerated irradiation with simultaneous integrated boost); CHRT was realized with CONV fractionation. The detailed description of the fractionation schemes and the analysis of their impact on the metabolic profile of blood serum are available in [ 45 ]. The RT and CHRT subgroups show significant differences in tumor localization and disease advancement ( Table 1 ).…”

“…We applied our standard measurement protocol [ 45 , 46 , 47 , 48 ]. The 1 H NMR spectra were acquired on a Bruker 400 MHz Avance III spectrometer (Bruker Biospin, Rheinstetten, Germany) equipped with a 5 mm PABBI probe.…”

“…To the best of our knowledge, this is the first attempt to characterize the pain and distress accumulated with the disease and its treatment in the patients with HNSCC. In these patients, we have previously successfully used NMR-based metabolomics to identify the radiotherapy- [ 45 ] and chemotherapy [ 46 ]-induced changes in blood serum as well as to describe the metabolic profile of treatment-induced toxicity [ 47 , 48 ]. The objective of the present study is to evaluate whether and to what extent the magnitude and duration of the distress and pain during the anticancer treatment affect the metabolic profile of the blood serum.…”