Serum‐plasma matched metabolomics for comprehensive characterization of benign thyroid nodule and papillary thyroid carcinoma

• Published in: International journal of cancer Vol. 144; no. 4; pp. 868 - 876
• Main Authors: Huang, Feng‐Qing, Li, Jing, Jiang, Lin, Wang, Feng‐Xiang, Alolga, Raphael N., Wang, Ma‐Jie, Min, Wen‐Jian, Ma, Gaoxiang, Zhao, Yi‐Jing, Wang, Shi‐Lei, Yu, Yuan, Chen, Xiang, Zhu, Danxia, Zhu, Jun, Wang, Guangzhou, Xia, Tiansong, Sang, Jian‐Feng, Lai, Mao‐De, Li, Ping, Zhu, Wei, Qi, Lian‐Wen
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15-02-2019; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Aged; Amino acids; Benign; Betaine; biomarkers; Biomarkers, Tumor - blood; Cancer; Child; Diagnosis, Differential; Differential diagnosis; Female; Glutamic acid; Glutamine; Humans; Inositol; Lipid metabolism; Liquid chromatography; Male; Medical research; Metabolic pathways; Metabolism; Metabolites; Metabolomics; Metabolomics - methods; Middle Aged; Nodules; non‐invasive diagnosis; Papillary thyroid carcinoma; Pathogenesis; Phenotypes; Plasma; Proline; Quadrupoles; Statistical analysis; Thyroid; Thyroid cancer; Thyroid Cancer, Papillary - blood; Thyroid Cancer, Papillary - diagnosis; Thyroid Cancer, Papillary - metabolism; Thyroid Neoplasms - blood; Thyroid Neoplasms - diagnosis; Thyroid Neoplasms - metabolism; thyroid nodule; Thyroid Nodule - blood; Thyroid Nodule - diagnosis; Thyroid Nodule - metabolism; Young Adult; thyroid nodule; papillary thyroid carcinoma; metabolomics; non-invasive diagnosis; biomarkers
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.31925

Metabolomics offers a noninvasive methodology to identify metabolic markers for pathogenesis and diagnosis of diseases. This work aimed to characterize circulating metabolic signatures of benign thyroid nodule (BTN) and papillary thyroid carcinoma (PTC) via serum‐plasma matched metabolomics. A cohort of 1,540 serum‐plasma matched samples and 114 tissues were obtained from healthy volunteers, BTN and PTC patients enrolled from 6 independent centers. Untargeted metabolomics was determined by liquid chromatography‐quadrupole time‐of‐flight mass spectrometric and multivariate statistical analyses. The use of serum‐plasma matched samples afforded a broad‐scope detection of 1,570 metabolic features. Metabolic phenotypes revealed significant pattern differences for healthy versus BTN and healthy versus PTC. Perturbed metabolic pathways related mainly to amino acid and lipid metabolism. It is worth noting that, BTN and PTC showed no significant differences but rather overlap in circulating metabolic signatures, and this observation was replicated in all study centers. For differential diagnosis of healthy versus thyroid nodules (BTN + PTC), a panel of 6 metabolic markers, namely myo‐inositol, α‐N‐phenylacetyl‐L‐glutamine, proline betaine, L‐glutamic acid, LysoPC(18:0) and LysoPC(18:1) provided area under the curve of 97.68% in the discovery phase and predictive accuracies of 84.78–98.18% in the 4 validation centers. Taken together, serum‐plasma matched metabolomics showed significant differences in circulating metabolites for healthy versus nodules but not for BTN versus PTC. Our results highlight the true metabolic nature of thyroid nodules, and potentially decrease overtreatment that exposes patients to unnecessary risks.
What's new?
When thyroid nodules are classified “indeterminate,” is it better to wait and see, or take out the thyroid? Usually, doctors remove the thyroid, resulting in a lifetime of levothyroxine replacement, yet most often the nodules are not cancerous. Here, the authors investigated whether metabolic profile could give a more accurate prediction of whether a thyroid nodule is cancerous. They tested healthy patients, those with benign nodules, and those with papillary thyroid carcinoma. Healthy patients showed distinct differences from those with benign nodules and those with carcinomas, while significant overlap was observed between circulating metabolites from BTN and PTC patients.