Sialic Acid-Binding Immunoglobulin-Like Lectin1 as a Novel Predictive Biomarker for Relapse in Graves' Disease: A Multicenter Study

Koshi Hashimoto, Eijun Nishihara, Masako Matsumoto, Shunichi Matsumoto, Yasuyo Nakajima, Kazutaka Tsujimoto, Hajime Yamakage, Noriko Satoh-Asahara, Jaeduk Yoshimura Noh, Koichi Ito, Akira Miyauchi, Masatomo Mori, Masanobu Yamada, Yoshihiro Ogawa

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Abstract

BACKGROUND: There are currently no reliable biomarkers to predict relapse in Graves' disease (GD). In the present study, we investigated novel diagnostic biomarkers to predict the long-term remission of or relapse in GD. METHODS: A DNA microarray analysis was performed to examine gene expression in the peripheral leukocytes of a frequently relapsing patient with GD and a patient in long-term remission after the discontinuation of antithyroid drugs (ATDs). Based on the DNA microarray analysis, we focused on Sialic acid-binding immunoglobulin-like lectin1 (SIGLEC1) as a candidate novel biomarker to predict GD relapse. Three hundred and fifty-eight patients with GD in the thyroid clinics of four different hospitals in Japan were included in a cross-sectional study to establish whether SIGLEC1 mRNA levels distinguish GD relapse experience from long-term remission. An additional 55 patients with GD were enrolled in a prospective study to clarify whether SIGLEC1 mRNA levels at ATD discontinuation predict GD relapse. RESULTS: SIGLEC1 mRNA levels were significantly higher in patients with GD relapse experience than in those in long-term remission. Based on the receiver operating characteristic analysis, we found that high SIGLEC1 mRNA levels (≥258.9 copies) significantly distinguished GD relapse experience from long-term remission (p < 0.0001; sensitivity 66.7%, specificity 70.1%). In the prospective study, when the optimal cutoff value from the receiver operating characteristic curve analysis was applied to SIGLEC1 mRNA positivity at ATD discontinuation, SIGLEC1-positive patients (≥258.9 copies) showed a significantly higher cumulative risk of relapse than SIGLEC1-negative patients (<258.9 copies) (p = 0.022, the log-rank test). CONCLUSIONS: SIGLEC1 mRNA levels have potential as a novel predictive biomarker for GD relapse.

Original languageEnglish
Pages (from-to)50-59
Number of pages10
JournalThyroid : official journal of the American Thyroid Association
Volume28
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

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Graves Disease
N-Acetylneuraminic Acid
Multicenter Studies
Immunoglobulins
Biomarkers
Recurrence
Antithyroid Agents
Messenger RNA
Microarray Analysis
Oligonucleotide Array Sequence Analysis
ROC Curve
Prospective Studies
Japan
Thyroid Gland
Leukocytes
Cross-Sectional Studies
Gene Expression
Sensitivity and Specificity

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Sialic Acid-Binding Immunoglobulin-Like Lectin1 as a Novel Predictive Biomarker for Relapse in Graves' Disease : A Multicenter Study. / Hashimoto, Koshi; Nishihara, Eijun; Matsumoto, Masako; Matsumoto, Shunichi; Nakajima, Yasuyo; Tsujimoto, Kazutaka; Yamakage, Hajime; Satoh-Asahara, Noriko; Noh, Jaeduk Yoshimura; Ito, Koichi; Miyauchi, Akira; Mori, Masatomo; Yamada, Masanobu; Ogawa, Yoshihiro.

In: Thyroid : official journal of the American Thyroid Association, Vol. 28, No. 1, 01.01.2018, p. 50-59.

Research output: Contribution to journalArticle

Hashimoto, K, Nishihara, E, Matsumoto, M, Matsumoto, S, Nakajima, Y, Tsujimoto, K, Yamakage, H, Satoh-Asahara, N, Noh, JY, Ito, K, Miyauchi, A, Mori, M, Yamada, M & Ogawa, Y 2018, 'Sialic Acid-Binding Immunoglobulin-Like Lectin1 as a Novel Predictive Biomarker for Relapse in Graves' Disease: A Multicenter Study', Thyroid : official journal of the American Thyroid Association, vol. 28, no. 1, pp. 50-59. https://doi.org/10.1089/thy.2017.0244
Hashimoto, Koshi ; Nishihara, Eijun ; Matsumoto, Masako ; Matsumoto, Shunichi ; Nakajima, Yasuyo ; Tsujimoto, Kazutaka ; Yamakage, Hajime ; Satoh-Asahara, Noriko ; Noh, Jaeduk Yoshimura ; Ito, Koichi ; Miyauchi, Akira ; Mori, Masatomo ; Yamada, Masanobu ; Ogawa, Yoshihiro. / Sialic Acid-Binding Immunoglobulin-Like Lectin1 as a Novel Predictive Biomarker for Relapse in Graves' Disease : A Multicenter Study. In: Thyroid : official journal of the American Thyroid Association. 2018 ; Vol. 28, No. 1. pp. 50-59.
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abstract = "BACKGROUND: There are currently no reliable biomarkers to predict relapse in Graves' disease (GD). In the present study, we investigated novel diagnostic biomarkers to predict the long-term remission of or relapse in GD. METHODS: A DNA microarray analysis was performed to examine gene expression in the peripheral leukocytes of a frequently relapsing patient with GD and a patient in long-term remission after the discontinuation of antithyroid drugs (ATDs). Based on the DNA microarray analysis, we focused on Sialic acid-binding immunoglobulin-like lectin1 (SIGLEC1) as a candidate novel biomarker to predict GD relapse. Three hundred and fifty-eight patients with GD in the thyroid clinics of four different hospitals in Japan were included in a cross-sectional study to establish whether SIGLEC1 mRNA levels distinguish GD relapse experience from long-term remission. An additional 55 patients with GD were enrolled in a prospective study to clarify whether SIGLEC1 mRNA levels at ATD discontinuation predict GD relapse. RESULTS: SIGLEC1 mRNA levels were significantly higher in patients with GD relapse experience than in those in long-term remission. Based on the receiver operating characteristic analysis, we found that high SIGLEC1 mRNA levels (≥258.9 copies) significantly distinguished GD relapse experience from long-term remission (p < 0.0001; sensitivity 66.7{\%}, specificity 70.1{\%}). In the prospective study, when the optimal cutoff value from the receiver operating characteristic curve analysis was applied to SIGLEC1 mRNA positivity at ATD discontinuation, SIGLEC1-positive patients (≥258.9 copies) showed a significantly higher cumulative risk of relapse than SIGLEC1-negative patients (<258.9 copies) (p = 0.022, the log-rank test). CONCLUSIONS: SIGLEC1 mRNA levels have potential as a novel predictive biomarker for GD relapse.",
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AU - Matsumoto, Masako

AU - Matsumoto, Shunichi

AU - Nakajima, Yasuyo

AU - Tsujimoto, Kazutaka

AU - Yamakage, Hajime

AU - Satoh-Asahara, Noriko

AU - Noh, Jaeduk Yoshimura

AU - Ito, Koichi

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N2 - BACKGROUND: There are currently no reliable biomarkers to predict relapse in Graves' disease (GD). In the present study, we investigated novel diagnostic biomarkers to predict the long-term remission of or relapse in GD. METHODS: A DNA microarray analysis was performed to examine gene expression in the peripheral leukocytes of a frequently relapsing patient with GD and a patient in long-term remission after the discontinuation of antithyroid drugs (ATDs). Based on the DNA microarray analysis, we focused on Sialic acid-binding immunoglobulin-like lectin1 (SIGLEC1) as a candidate novel biomarker to predict GD relapse. Three hundred and fifty-eight patients with GD in the thyroid clinics of four different hospitals in Japan were included in a cross-sectional study to establish whether SIGLEC1 mRNA levels distinguish GD relapse experience from long-term remission. An additional 55 patients with GD were enrolled in a prospective study to clarify whether SIGLEC1 mRNA levels at ATD discontinuation predict GD relapse. RESULTS: SIGLEC1 mRNA levels were significantly higher in patients with GD relapse experience than in those in long-term remission. Based on the receiver operating characteristic analysis, we found that high SIGLEC1 mRNA levels (≥258.9 copies) significantly distinguished GD relapse experience from long-term remission (p < 0.0001; sensitivity 66.7%, specificity 70.1%). In the prospective study, when the optimal cutoff value from the receiver operating characteristic curve analysis was applied to SIGLEC1 mRNA positivity at ATD discontinuation, SIGLEC1-positive patients (≥258.9 copies) showed a significantly higher cumulative risk of relapse than SIGLEC1-negative patients (<258.9 copies) (p = 0.022, the log-rank test). CONCLUSIONS: SIGLEC1 mRNA levels have potential as a novel predictive biomarker for GD relapse.

AB - BACKGROUND: There are currently no reliable biomarkers to predict relapse in Graves' disease (GD). In the present study, we investigated novel diagnostic biomarkers to predict the long-term remission of or relapse in GD. METHODS: A DNA microarray analysis was performed to examine gene expression in the peripheral leukocytes of a frequently relapsing patient with GD and a patient in long-term remission after the discontinuation of antithyroid drugs (ATDs). Based on the DNA microarray analysis, we focused on Sialic acid-binding immunoglobulin-like lectin1 (SIGLEC1) as a candidate novel biomarker to predict GD relapse. Three hundred and fifty-eight patients with GD in the thyroid clinics of four different hospitals in Japan were included in a cross-sectional study to establish whether SIGLEC1 mRNA levels distinguish GD relapse experience from long-term remission. An additional 55 patients with GD were enrolled in a prospective study to clarify whether SIGLEC1 mRNA levels at ATD discontinuation predict GD relapse. RESULTS: SIGLEC1 mRNA levels were significantly higher in patients with GD relapse experience than in those in long-term remission. Based on the receiver operating characteristic analysis, we found that high SIGLEC1 mRNA levels (≥258.9 copies) significantly distinguished GD relapse experience from long-term remission (p < 0.0001; sensitivity 66.7%, specificity 70.1%). In the prospective study, when the optimal cutoff value from the receiver operating characteristic curve analysis was applied to SIGLEC1 mRNA positivity at ATD discontinuation, SIGLEC1-positive patients (≥258.9 copies) showed a significantly higher cumulative risk of relapse than SIGLEC1-negative patients (<258.9 copies) (p = 0.022, the log-rank test). CONCLUSIONS: SIGLEC1 mRNA levels have potential as a novel predictive biomarker for GD relapse.

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