Comparative assessment of Graves' disease and main extrathyroidal manifestation, Graves' ophthalmopathy, by non-targeted metabolite profiling of blood and orbital tissue

Dong Yoon Ji, Se Hee Park, Soo Jin Park, Kyoung Heon Kim, Cheol Ryong Ku, Dong Yeob Shin, Jin Sook Yoon, Do Yup Lee, Eun Jig Lee

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Graves' disease (GD) is an autoimmune disorder that causes the overproduction of thyroid hormones and consequent cascade of systemic metabolism dysfunction. Moreover, Graves' ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). The goal of the study was to identify metabolic signatures in association with diagnostic biomarkers of GD without GO and GO, respectively. Ninety metabolites were profiled and analyzed based on a non-targeted primary metabolite profiling from plasma samples of 21 GD patients without GO, 26 subjects with GO, and 32 healthy subjects. Multivariate statistics showed a clear discrimination between healthy controls and disease group (R2Y = 0.518, Q2 = 0.478) and suggested a biomarker panel consisting of 10 metabolites. Among them, most of metabolites showed the positive association with the levels of thyrotropin receptor antibodies. With combination of proline and 1,5-anhydroglucitol, which were identified as GO-specific modulators, the re-constructed biomarker model greatly improved the statistical power and also facilitated simultaneous discrimination among healthy control, GO, and GD without GO groups (AUC = 0.845-0.935). Finally, the comparative analysis of tissue metabolite profiles from GO patients proposed putative metabolic linkage between orbital adipose/connective tissues and the biofluidic consequences, in which fumarate, proline, phenylalanine, and glycerol were coordinately altered with the blood metabolites.

Original languageEnglish
Article number9262
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 2018 Dec 1

Fingerprint

Graves Ophthalmopathy
Graves Disease
Biomarkers
Proline
Thyrotropin Receptors
Fumarates
Phenylalanine
Thyroid Hormones
Connective Tissue
Glycerol
Area Under Curve
Adipose Tissue
Healthy Volunteers
Control Groups

ASJC Scopus subject areas

  • General

Cite this

Comparative assessment of Graves' disease and main extrathyroidal manifestation, Graves' ophthalmopathy, by non-targeted metabolite profiling of blood and orbital tissue. / Ji, Dong Yoon; Park, Se Hee; Park, Soo Jin; Kim, Kyoung Heon; Ku, Cheol Ryong; Shin, Dong Yeob; Yoon, Jin Sook; Lee, Do Yup; Lee, Eun Jig.

In: Scientific Reports, Vol. 8, No. 1, 9262, 01.12.2018.

Research output: Contribution to journalArticle

Ji, Dong Yoon ; Park, Se Hee ; Park, Soo Jin ; Kim, Kyoung Heon ; Ku, Cheol Ryong ; Shin, Dong Yeob ; Yoon, Jin Sook ; Lee, Do Yup ; Lee, Eun Jig. / Comparative assessment of Graves' disease and main extrathyroidal manifestation, Graves' ophthalmopathy, by non-targeted metabolite profiling of blood and orbital tissue. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{1e0a4be06e7b46c3ab8183d8cb869065,
title = "Comparative assessment of Graves' disease and main extrathyroidal manifestation, Graves' ophthalmopathy, by non-targeted metabolite profiling of blood and orbital tissue",
abstract = "Graves' disease (GD) is an autoimmune disorder that causes the overproduction of thyroid hormones and consequent cascade of systemic metabolism dysfunction. Moreover, Graves' ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). The goal of the study was to identify metabolic signatures in association with diagnostic biomarkers of GD without GO and GO, respectively. Ninety metabolites were profiled and analyzed based on a non-targeted primary metabolite profiling from plasma samples of 21 GD patients without GO, 26 subjects with GO, and 32 healthy subjects. Multivariate statistics showed a clear discrimination between healthy controls and disease group (R2Y = 0.518, Q2 = 0.478) and suggested a biomarker panel consisting of 10 metabolites. Among them, most of metabolites showed the positive association with the levels of thyrotropin receptor antibodies. With combination of proline and 1,5-anhydroglucitol, which were identified as GO-specific modulators, the re-constructed biomarker model greatly improved the statistical power and also facilitated simultaneous discrimination among healthy control, GO, and GD without GO groups (AUC = 0.845-0.935). Finally, the comparative analysis of tissue metabolite profiles from GO patients proposed putative metabolic linkage between orbital adipose/connective tissues and the biofluidic consequences, in which fumarate, proline, phenylalanine, and glycerol were coordinately altered with the blood metabolites.",
author = "Ji, {Dong Yoon} and Park, {Se Hee} and Park, {Soo Jin} and Kim, {Kyoung Heon} and Ku, {Cheol Ryong} and Shin, {Dong Yeob} and Yoon, {Jin Sook} and Lee, {Do Yup} and Lee, {Eun Jig}",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-27600-0",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Comparative assessment of Graves' disease and main extrathyroidal manifestation, Graves' ophthalmopathy, by non-targeted metabolite profiling of blood and orbital tissue

AU - Ji, Dong Yoon

AU - Park, Se Hee

AU - Park, Soo Jin

AU - Kim, Kyoung Heon

AU - Ku, Cheol Ryong

AU - Shin, Dong Yeob

AU - Yoon, Jin Sook

AU - Lee, Do Yup

AU - Lee, Eun Jig

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Graves' disease (GD) is an autoimmune disorder that causes the overproduction of thyroid hormones and consequent cascade of systemic metabolism dysfunction. Moreover, Graves' ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). The goal of the study was to identify metabolic signatures in association with diagnostic biomarkers of GD without GO and GO, respectively. Ninety metabolites were profiled and analyzed based on a non-targeted primary metabolite profiling from plasma samples of 21 GD patients without GO, 26 subjects with GO, and 32 healthy subjects. Multivariate statistics showed a clear discrimination between healthy controls and disease group (R2Y = 0.518, Q2 = 0.478) and suggested a biomarker panel consisting of 10 metabolites. Among them, most of metabolites showed the positive association with the levels of thyrotropin receptor antibodies. With combination of proline and 1,5-anhydroglucitol, which were identified as GO-specific modulators, the re-constructed biomarker model greatly improved the statistical power and also facilitated simultaneous discrimination among healthy control, GO, and GD without GO groups (AUC = 0.845-0.935). Finally, the comparative analysis of tissue metabolite profiles from GO patients proposed putative metabolic linkage between orbital adipose/connective tissues and the biofluidic consequences, in which fumarate, proline, phenylalanine, and glycerol were coordinately altered with the blood metabolites.

AB - Graves' disease (GD) is an autoimmune disorder that causes the overproduction of thyroid hormones and consequent cascade of systemic metabolism dysfunction. Moreover, Graves' ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). The goal of the study was to identify metabolic signatures in association with diagnostic biomarkers of GD without GO and GO, respectively. Ninety metabolites were profiled and analyzed based on a non-targeted primary metabolite profiling from plasma samples of 21 GD patients without GO, 26 subjects with GO, and 32 healthy subjects. Multivariate statistics showed a clear discrimination between healthy controls and disease group (R2Y = 0.518, Q2 = 0.478) and suggested a biomarker panel consisting of 10 metabolites. Among them, most of metabolites showed the positive association with the levels of thyrotropin receptor antibodies. With combination of proline and 1,5-anhydroglucitol, which were identified as GO-specific modulators, the re-constructed biomarker model greatly improved the statistical power and also facilitated simultaneous discrimination among healthy control, GO, and GD without GO groups (AUC = 0.845-0.935). Finally, the comparative analysis of tissue metabolite profiles from GO patients proposed putative metabolic linkage between orbital adipose/connective tissues and the biofluidic consequences, in which fumarate, proline, phenylalanine, and glycerol were coordinately altered with the blood metabolites.

UR - http://www.scopus.com/inward/record.url?scp=85048797041&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048797041&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-27600-0

DO - 10.1038/s41598-018-27600-0

M3 - Article

C2 - 29915201

AN - SCOPUS:85048797041

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 9262

ER -