Serum-based metabolic alterations in patients with papillary thyroid carcinoma unveiled by non-targeted 1H-NMR metabolomics approach

Objective(s): As the most prevalent endocrine system malignancy, papillary thyroid carcinoma had a very fast rising incidence in recent years for unknown reasons besides the fact that the current methods in thyroid cancer diagnosis still hold some limitations. Therefore, the aim of this study was to improve the potential molecular markers for diagnosis of benign and malignant thyroid nodules to prevent unnecessary surgeries for benign tumors. Materials and Methods: In this study, 1H-NMR metabolomics platform was used to seek the discriminating serum metabolites in malignant papillary thyroid carcinoma (PTC) compared to benign multinodular goiter (MNG) and healthy subjects and also to better understand the disease mechanisms using bioinformatics analysis. Multivariate statistical analysis showed that PTC and MNG samples could be successfully discriminated in PCA and OPLS-DA score plots. Results: Significant metabolites that differentiated malignant and benign thyroid lesions included citrate, acetylcarnitine, glutamine, homoserine, glutathione, kynurenine, nicotinic acid, hippurate, tyrosine, tryptophan, β-alanine, and xanthine. The significant metabolites in the PTC group compared to healthy subjects also included scyllo- and myo-inositol, tryptophan, propionate, lactate, homocysteine, 3-methyl glutaric acid, asparagine, aspartate, choline, and acetamide. The metabolite sets enrichment analysis demonstrated that aspartate metabolism and urea cycle were the most important pathways in papillary thyroid cancer progression. Conclusion: The study results demonstrated that serum metabolic fingerprinting could serve as a viable method for differentiating various thyroid lesions and for proposing novel potential markers for thyroid cancers. Obviously, further studies are needed for the validation of the results.