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

Author(s)

dos Reis, Mariana Bisarro ^{[1, 2, 3]} ; Barros-Filho, Mateus Camargo ^{[1, 2]} ; Marchi, Fabio Albuquerque ^{[1, 2]} ; Beltrami, Caroline Moraes ^{[1, 2]} ; Kuasne, Hellen ^{[1, 2]} ; Lopes Pinto, Clovis Antonio ^[4] ; Ambatipudi, Srikant ^{[5, 6]} ; Herceg, Zdenko ^[5] ; Kowalski, Luiz Paulo ^[7] ; Rogatto, Silvia Regina ^{[3, 8, 9]}

Affiliation

^[1] AC Camargo Canc Ctr, CIPE, Int Res Ctr, BR-01509010 Sao Paulo, SP - Brazil

^[2] Natl Inst Sci & Technol Oncogen, BR-01509010 Sao Paulo, SP - Brazil

^[3] Sao Paulo State Univ, Dept Urol, Fac Med, UNESP, BR-18618970 Botucatu, SP - Brazil

^[4] AC Camargo Canc Ctr, Dept Pathol, BR-01509010 Sao Paulo, SP - Brazil

^[5] IARC, Epigenet Grp, F-69372 Lyon - France

^[6] Univ Bristol, Integrat Epidemiol Unit, MRC, Bristol BS8 1TH, Avon - England

^[7] AC Camargo Canc Ctr, Dept Head & Neck Surg & Otorhinolaryngol, BR-01509010 Sao Paulo, SP - Brazil

^[8] Univ Southern Denmark, Dept Clin Genet, Vejle Hosp, DK-7100 Vejle - Denmark

^[9] Univ Southern Denmark, Inst Reg Hlth Res, Vejle Hosp, DK-7100 Vejle - Denmark

• Document type: Journal article
• Source: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM; v. 102, n. 11, p. 4089-4099, NOV 1 2017.
• Web of Science Citations: 12

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 Hurthle 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. (AU)

• FAPESP's process: 15/20748-5 - Diagnostic and prognostic markers useful in the clinical practice for patients with thyroid nodules: validation of previous findings and functional studies
• Grantee: Silvia Regina Rogatto
• Support type: Regular Research Grants
• FAPESP's process: 08/57887-9 - National Institute of Oncogenomics
• Grantee: Luiz Paulo Kowalski
• Support type: Research Projects - Thematic Grants