LC-MS-based serum metabolomics analysis and potential biomarkers for oxaliplatin induced neurotoxicity in colorectal cancer

Abstract

Oxapliplatin-induced peripheral neuropathy (OIPN) is a significant adverse effect encountered in patients with colorectal cancer undergoing oxaliplatin therapy. However, the pathogenesis of OIPN remains unclear. This study aimed to identify potential diagnostic biomarkers for OIPN and discover the metabolic pathways associated with the disease. Serum samples were collected from 218 subjects, including patients with OIPN and control (CONT). The metabolite profiles were analyzed using nontargeted liquid chromatography-mass spectrometry (LC-MS) serum metabolomics method. Subsequently, differentially altered metabolites were identified and evaluated through multivariate statistical analyses. In this study, patients with OIPN and CONT were distinguished by ten significant metabolites. The levels of racemethionine, O-acetylcarnitine, stearolic acid, aminoadipic acid, iminoarginine, galactaric acid, and all-trans-retinoic acid were increased, whereas the levels of 3-methyl-L-tyrosine, 5-aminopentanoic acid, and erythritol compared were found to be diminished in patients with OIPN when compared to the CONT. Through receiver operating characteristic (ROC) curve analysis, racemethionine, stearolic acid, 5-aminopentanoic acid, erythritol, aminoadipic acid, and all-trans-retinoic acid were pinpointed as promising biomarkers for OIPN. Significantly altered pathways included amino acids (arginine biosynthesis, beta-alanine metabolism, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, lysine degradation, and phenylalanine, tyrosine and tryptophan biosynthesis), lipid (linoleic acid metabolism and the biosynthesis of unsaturated fatty acids), and energy metabolism. This study, by identifying serum biomarkers and dissecting metabolic pathways, offers a groundbreaking perspective on the susceptibility mechanisms underlying OIPN. It stands as an invaluable resource for the adjunctive diagnosis of OIPN, with the potential to diminish the incidence of adverse reactions and to enhance the objectivity and reliability of clinical diagnoses of OIPN.