Serum Unsaturated Free Fatty Acids: A Potential Biomarker Panel for Differentiating Benign Thyroid Diseases from Thyroid Cancer

Background: Serum free fatty acids (FFAs) are correlated with pathological status, and change in serum FFA levels may be associated with thyroid diseases. Materials and Methods: In this study, 664 serum samples from 322 healthy controls, 129 patients with benign thyroid disease (BTD), and 213 patients with thyroid cancer (TC) were collected. Chip-based direct-infusion nanoelectrospray-mass spectrometry was performed to simultaneously quantify six serum FFAs (i.e., C(16:1), C(18:1), C(18:2), C(18:3), C(20:4), and C(22:6).), with the excellent correlation coefficients of > 0.99 and relative standard deviation of <18% for all analysts. The Mann-Whitney U test was used to compare the differences in serum FFA levels between three above-mentioned groups. Results: Significant increase in the levels of C(16:1), C(18:1), C(18:2), C(18:3), C(20:4), and C(22:6) in healthy controls relative to TC patients and BTD patients was observed, and the levels of C(16:1), C(18:2), C(20:4), and C(22:6) in BTD patients were significantly decreased relative to TC patients. Receiver operating characteristic (ROC) analysis indicated that a combination of C(16:1), C(18:2), C(20:4), and C(22:6) has excellent diagnostic performance to differentiate BTD patients from TC patients, with an area under the ROC curve of 0.857, a sensitivity of 76.8%, and a specificity of 83.7%. Conclusions: Change in serum levels of FFAs is closely correlated with thyroid diseases, and a biomarker panel (C(16:1), C(18:2), C(20:4), and C(22:6)) should be of benefit to differentiate BTD patients from TC patients.