Correlation between the expression of metabolites and acute radiation enteritis in patients with cervical cancer

Objective To investigate the relationship between the metabolites in the fecal samples from cervical cancer patients and radiation-induced acute intestinal symptoms during radiotherapy. Methods A total of 51 cervical cancer patients who received radiotherapy in our hospital from September 2017 to June 2018 were enrolled. One patient was excluded due to efficiant sample failure, so a total of 50 patients were included in the study. Totally 200 fecal samples were collected at four time points, i. e. before radiotherapy, 2 weeks post radiotherapy starting, 4 weeks post radiotherapy starting and end of radiotherapy. These fecal samples were analyzed by non-targeted metabolomics using liquid chromatography-mass spectrometry (LC-MS). Data were analyzed with statistical method including partial least squares-discriminant analysis (PLS-DA), agglomerate hierarchical clustering to investigate the trend of metabolites expression in feces. Results A total of 5 770 metabolic peaks were detected and 121 biomarkers were identified, of which 77 biomarkers were up-regulated and 44 biomarkers were down-regulated. Nineteen biomarkers were significantly changed at four time points after radiotherapy, including 1-methylxanthine, linoleic acid, 5-aminopentanoic acid, phenethylamine, styrene, N-acetylglutamate, nandrolone, 4-acetylaminobutyric acid, N-acetyl-L-phenylalanine, daidzein, cholic acid, arachidonic acid, methyl leucine, N-formyl-L-methionine, quercetin, phenylalanine, gluconic acid, melibiose and α-CMBHC. Four metabolic pathways of phenylalanine tyrosine, niacin and nicotinamide, linoleic acid and lysine degradation (Pathway imPact >0.1) were found to be related to acute radiation enteritis. Conclusions The metabolites in the feces of cervical cancer patients change significantly during radiotherapy, and some biomarkers in the fecal supernatant are up- or down-regulated to varying degrees as doses increase, which provides new ideas and method for the prediction of acute radiation enteritis. Key words: Cervical cancer; Metabolomics; Radiation-induced acute intestinal symptoms