Metabolomic profiles of thyroid nodules using nuclear magnetic resonance analysis of percutaneous fine needle aspiration specimens: Potential application for the diagnosis of papillary thyroid carcinoma
갑상선 결절의 경피적 세침 흡인물에 대한 핵 자기 공명 대사체학적 성분 분석: 갑상선 유두암 진단 방법으로서의 가능성 평가

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의과대학 의학과
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서울대학교 대학원
학위논문 (박사)-- 서울대학교 대학원 : 의학과, 2014. 2. 김현진.
Introduction: Cytopathologic analysis of fine needle aspiration biopsy (FNAB) specimens is the standard diagnostic test for thyroid nodules. However, its accuracy and adequacy has been reported to be limited for the diagnosis of thyroid nodules. The purpose of this study is to present the differences in the metabolomic profiles of malignant (papillary thyroid carcinoma [PTC]) and benign thyroid nodules using metabolomic analysis (nuclear magnetic resonance [NMR]) of FNAB specimens of thyroid nodules and to evaluate the potential of the metabolomic approach (NMR) as an ancillary method for diagnosing PTC.

Methods: In total, 230 samples from patients with thyroid nodules were collected by ultrasonography-guided percutaneous FNAB
among them, 35 samples diagnosed as malignant (PTC) and 69 samples diagnosed as benign follicular nodules on conventional cytopathologic analysis were spectroscopically analyzed using 1.7 mm tube NMR. Metabolomic profiles were statistically generated based on the NMR results, and their correlation with conventional cytopathologic diagnoses from the same samples were assessed to determine the feasibility of using these profiles as a diagnostic tool for thyroid nodules. Furthermore, we analyzed the correlation between the metabolomic profiles of surgically confirmed 25 PTC samples and clinicopathologic factors such as tumor multiplicity, T stage, N stage, and BRAF mutation status.

Results: Benign nodules and PTCs could be distinguished according to the different relative concentrations of several metabolites. The citrate (2.6 ppm), glutamate (2.0 ppm), and glutamine (2.1 ppm) levels in benign samples were greater than those in PTC samples and the lactate (1.3 ppm) and choline (3.2 ppm) levels in PTC samples were greater than those in benign samples. Receiver operating characteristic (ROC) curve analysis indicated that seven metabolites could serve as discriminators (area under the ROC curve value, 0.64-0.85), of which citrate was the most significant discriminator.
However, in PTC subgroup analysis, we did not observe a significant correlation between clinicopathologic factors and metabolomic profiles.

Conclusions: This study results indicate the potential of the metabolomic approach (NMR) as an ancillary method for diagnosing PTC using FNAB specimens of thyroid nodules.
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Ph.D. / Sc.D._의학과)
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