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

Abstract

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, 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.

Metabolite analysis-aided diagnosis of papillary thyroid cancer

“…Veyrat-Durebex et al conveyed a metabolomic study on metabolomics signatures with a subset of RET variants according to their oncogenic risk level and demonstrated the efficacy of metabolomics in testing RET mutations' pathogenicity (Veyrat-Durebex et al 2019). A serumplasma-matched untargeted metabolomics study was conducted to reveal the significant metabolic pattern differences of BTN and PTC, and no significant difference was found in circulating metabolic signatures between BTN and PTC (Huang et al 2019). For differential diagnosis of HC versus BTN and PTC, a panel of six metabolic markers, namely myo-inositol, N-phenylacetyl-Lglutamine, proline betaine, l-glutamic acid, LysoPC (18:0) and LysoPC (18:1) provided AUC of 97.68% in discovery phase and predictive accuracies of 84.78-98.18% (Huang et al 2019).…”

Identification of Potential Radiation Responsive Metabolic Biomarkers in Plasma of Rats Exposed to Different Doses of Cobalt-60 Gamma Rays

“…13,14 Metabolomics based on mass spectrometry (MS) platforms has shown great potential to explore the biomarkers of radiation damage due to high-throughput and minimally invasive sample collection methods. 15,16 Over the last decade, metabolomics studies have been conducted using rodent, 17,18 non-human primates, 19,20 and humans 21,22 to explore IR-induced potential biomarkers. These studies have confirmed a large number of metabolites are altered after exposure to IR.…”

<p>The Blood Biomarkers of Thyroid Cancer</p>

“…Therefore, non-invasive blood tests based on metabolomics are not suitable for their differential diagnosis. 11 But Wojakowska's and Guo's research has yielded different results. Wojakowska's 12 research using tissues as the material, reached similar conclusions as Guo's 13 which used serum and tissue as the material.…”