Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors

Mariana Bisarro Dos Reis; Mateus Camargo Barros-Filho; Fábio Albuquerque Marchi; Caroline Moraes Beltrami; Hellen Kuasne; Clóvis Antônio Lopes Pinto; Srikant Ambatipudi; Zdenko Herceg; Luiz Paulo Kowalski; Silvia Regina Rogatto

doi:10.1210/jc.2017-00881

Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors

Mariana Bisarro Dos Reis, Mateus Camargo Barros-Filho, Fábio Albuquerque Marchi, Caroline Moraes Beltrami, Hellen Kuasne, Clóvis Antônio Lopes Pinto, Srikant Ambatipudi, Zdenko Herceg, Luiz Paulo Kowalski, Silvia Regina Rogatto

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Abstract

Context: Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis.

Objective: To identify a prognostic epigenetic signature in thyroid cancer.

Design: Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database.

Results: A specific epigenetic profile was detected according to each histological subtype. BTLs and follicular carcinomas showed a greater number of methylated CpG in comparison with NTs, whereas hypomethylation was predominant in papillary and undifferentiated carcinomas. A prognostic classifier based on 21 DNA methylation probes was able to predict poor outcome in patients with WDTC (sensitivity 63%, specificity 92% for internal data; sensitivity 64%, specificity 88% for TCGA data). High-risk score based on the classifier was considered an independent factor of poor outcome (Cox regression, P < 0.001).

Conclusions: The methylation profile of thyroid lesions exhibited a specific signature according to the histological subtype. A meaningful algorithm composed of 21 probes was capable of predicting the recurrence in WDTC.

Original language	English
Pages (from-to)	4089-4099
Number of pages	11
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	102
Issue number	11
DOIs	https://doi.org/10.1210/jc.2017-00881
Publication status	Published - 1 Nov 2017

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MRC UoB UNITE Unit - Programme 2
Relton, C. L. & Relton, C. L.
1/06/13 → 31/03/18
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Bisarro Dos Reis, M., Barros-Filho, M. C., Marchi, F. A., Beltrami, C. M., Kuasne, H., Pinto, C. A. L., Ambatipudi, S., Herceg, Z., Kowalski, L. P., & Rogatto, S. R. (2017). Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors. Journal of Clinical Endocrinology and Metabolism, 102(11), 4089-4099. https://doi.org/10.1210/jc.2017-00881

Bisarro Dos Reis, Mariana ; Barros-Filho, Mateus Camargo ; Marchi, Fábio Albuquerque ; Beltrami, Caroline Moraes ; Kuasne, Hellen ; Pinto, Clóvis Antônio Lopes ; Ambatipudi, Srikant ; Herceg, Zdenko ; Kowalski, Luiz Paulo ; Rogatto, Silvia Regina. / Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors. In: Journal of Clinical Endocrinology and Metabolism. 2017 ; Vol. 102, No. 11. pp. 4089-4099.

@article{850cd6e3065d4fcdadf6df5d310e110c,

title = "Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors",

abstract = "Context: Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis.Objective: To identify a prognostic epigenetic signature in thyroid cancer.Design: Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 H{\"u}rthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database.Results: A specific epigenetic profile was detected according to each histological subtype. BTLs and follicular carcinomas showed a greater number of methylated CpG in comparison with NTs, whereas hypomethylation was predominant in papillary and undifferentiated carcinomas. A prognostic classifier based on 21 DNA methylation probes was able to predict poor outcome in patients with WDTC (sensitivity 63%, specificity 92% for internal data; sensitivity 64%, specificity 88% for TCGA data). High-risk score based on the classifier was considered an independent factor of poor outcome (Cox regression, P < 0.001).Conclusions: The methylation profile of thyroid lesions exhibited a specific signature according to the histological subtype. A meaningful algorithm composed of 21 probes was capable of predicting the recurrence in WDTC.",

author = "{Bisarro Dos Reis}, Mariana and Barros-Filho, {Mateus Camargo} and Marchi, {F{\'a}bio Albuquerque} and Beltrami, {Caroline Moraes} and Hellen Kuasne and Pinto, {Cl{\'o}vis Ant{\^o}nio Lopes} and Srikant Ambatipudi and Zdenko Herceg and Kowalski, {Luiz Paulo} and Rogatto, {Silvia Regina}",

year = "2017",

month = nov,

day = "1",

doi = "10.1210/jc.2017-00881",

language = "English",

volume = "102",

pages = "4089--4099",

journal = "Journal of Clinical Endocrinology and Metabolism",

issn = "0021-972X",

publisher = "Oxford University Press",

number = "11",

}

Bisarro Dos Reis, M, Barros-Filho, MC, Marchi, FA, Beltrami, CM, Kuasne, H, Pinto, CAL, Ambatipudi, S, Herceg, Z, Kowalski, LP & Rogatto, SR 2017, 'Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors', Journal of Clinical Endocrinology and Metabolism, vol. 102, no. 11, pp. 4089-4099. https://doi.org/10.1210/jc.2017-00881

Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors. / Bisarro Dos Reis, Mariana; Barros-Filho, Mateus Camargo; Marchi, Fábio Albuquerque; Beltrami, Caroline Moraes; Kuasne, Hellen; Pinto, Clóvis Antônio Lopes; Ambatipudi, Srikant; Herceg, Zdenko; Kowalski, Luiz Paulo; Rogatto, Silvia Regina.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 102, No. 11, 01.11.2017, p. 4089-4099.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors

AU - Bisarro Dos Reis, Mariana

AU - Barros-Filho, Mateus Camargo

AU - Marchi, Fábio Albuquerque

AU - Beltrami, Caroline Moraes

AU - Kuasne, Hellen

AU - Pinto, Clóvis Antônio Lopes

AU - Ambatipudi, Srikant

AU - Herceg, Zdenko

AU - Kowalski, Luiz Paulo

AU - Rogatto, Silvia Regina

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Context: Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis.Objective: To identify a prognostic epigenetic signature in thyroid cancer.Design: Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database.Results: A specific epigenetic profile was detected according to each histological subtype. BTLs and follicular carcinomas showed a greater number of methylated CpG in comparison with NTs, whereas hypomethylation was predominant in papillary and undifferentiated carcinomas. A prognostic classifier based on 21 DNA methylation probes was able to predict poor outcome in patients with WDTC (sensitivity 63%, specificity 92% for internal data; sensitivity 64%, specificity 88% for TCGA data). High-risk score based on the classifier was considered an independent factor of poor outcome (Cox regression, P < 0.001).Conclusions: The methylation profile of thyroid lesions exhibited a specific signature according to the histological subtype. A meaningful algorithm composed of 21 probes was capable of predicting the recurrence in WDTC.

AB - Context: Even though the majority of well-differentiated thyroid carcinoma (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidence suggests that the deregulation of DNA methylation has the potential to point out molecular markers associated with worse prognosis.Objective: To identify a prognostic epigenetic signature in thyroid cancer.Design: Genome-wide DNA methylation assays (450k platform, Illumina) were performed in a cohort of 50 nonneoplastic thyroid tissues (NTs), 17 benign thyroid lesions (BTLs), and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated, and 3 anaplastic). A prognostic classifier for WDTC was developed via diagonal linear discriminant analysis. The results were compared with The Cancer Genome Atlas (TCGA) database.Results: A specific epigenetic profile was detected according to each histological subtype. BTLs and follicular carcinomas showed a greater number of methylated CpG in comparison with NTs, whereas hypomethylation was predominant in papillary and undifferentiated carcinomas. A prognostic classifier based on 21 DNA methylation probes was able to predict poor outcome in patients with WDTC (sensitivity 63%, specificity 92% for internal data; sensitivity 64%, specificity 88% for TCGA data). High-risk score based on the classifier was considered an independent factor of poor outcome (Cox regression, P < 0.001).Conclusions: The methylation profile of thyroid lesions exhibited a specific signature according to the histological subtype. A meaningful algorithm composed of 21 probes was capable of predicting the recurrence in WDTC.

U2 - 10.1210/jc.2017-00881

DO - 10.1210/jc.2017-00881

M3 - Article (Academic Journal)

C2 - 28938489

AN - SCOPUS:85037977822

VL - 102

SP - 4089

EP - 4099

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 11

ER -

Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors

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MRC UoB UNITE Unit - Programme 2

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