Prognostic classifier based on genome-wide DNA methylation profiling in well-differentiated thyroid tumors.

Prognostic classifier based on genome-wide DNA methylation profiling in well-differentiated thyroid tumors.

J Clin Endocrinol Metab. 2017 Aug 16;:

Authors: Dos Reis MB, Barros-Filho MC, Marchi FA, Beltrami CM, Kuasne H, Pinto CAL, Ambatipudi S, Herceg Z, Kowalski LP, Rogatto SR

Abstract
Context: Even though the majority of well-differentiated thyroid cancer (WDTC) is indolent, a number of cases display an aggressive behavior. Cumulative evidences have suggested 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 non-neoplastic thyroid tissues (NT), 17 benign thyroid lesions (BTL) and 74 thyroid carcinomas (60 papillary, 8 follicular, 2 Hürthle cell, 1 poorly differentiated and 3 anaplastic). A prognostic classifier for WDTC was developed using 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. Benign lesions and follicular carcinomas showed a greater number of methylated CpG in comparison with NT, 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 by 21 probes was capable of predicting the recurrence in WDTC.

PMID: 28938489 [PubMed - as supplied by publisher]

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