Non-invasive detection of metastatic papillary thyroid carcinoma after radical surgery using salivary metabolomic biomarkers

OBJECTIVE: Accurate assessment of metastatic status is crucial for determining radioactive iodine (RAI) dosing in postoperative papillary thyroid carcinoma (PTC) patients. This study aimed to identify unbiased biomarkers in metastatic PTC patients after surgery by applying a metabolomics workflow in saliva samples. MATERIALS AND METHODS: Saliva samples from 70 postoperative PTC patients (35 metastatic PTC patients in metastasis group and 35 non-metastatic PTC patients in control group) were analyzed using liquid chromatography - mass spectrometry. Orthogonal partial least-squares-discriminant analysis was applied to identify differential metabolites and significant pathways were examined within these metabolites. Receiver operating characteristic curve (ROC) analysis was utilized to further evaluate the diagnostic performance of candidate metabolites. RESULTS: A total of 119 differential metabolites were identified, with 108 upregulated and 11 downregulated. Pathway analysis revealed 13 significantly dysregulated metabolic pathways in metastatic PTC, including necroptosis, choline metabolism in cancer, sphingolipid signaling, valine, leucine and isoleucine biosynthesis, linoleic acid metabolism and pantothenate and CoA biosynthesis. ROC analysis demonstrated six discriminating biomarkers (5 lipids, 1 amine) that effectively distinguished metastatic from non-metastatic PTC, with all area under the curve values exceeding 0.8. Notably, these metabolites maintained diagnostic performance even in the thyroglobulin antibody-positive subgroup (≥ 4.11 IU/mL) for metastatic screening. CONCLUSION: This study demonstrates the potential of salivary biomarkers as a non-invasive diagnostic approach for metastatic PTC to aid the appropriate dosing for RAI therapy. It also offers new insights into the mechanisms of PTC metastasis and potential targets for adjuvant therapy.