GADD45B Transcript Is a Prognostic Marker in Papillary Thyroid Carcinoma Patients Treated With Total Thyroidectomy and Radioiodine Therapy

Author(s)

Barros-Filho, Mateus C. ^[1] ; de Mello, Julia B. H. ^[1] ; Marchi, Fabio A. ^[1] ; Pinto, Clovis A. L. ^[2] ; da Silva, Igor C. ^[3] ; Damasceno, Patricia K. F. ^[4] ; Soares, Milena B. P. ^{[4, 5]} ; Kowalski, Luiz P. ^[6] ; Rogatto, Silvia R. ^[7]

Affiliation

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

^[2] AC Camargo Canc Ctr, Dept Pathol, Sao Paulo - Brazil

^[3] Sao Rafael Hosp, Dept Pathol, Salvador, BA - Brazil

^[4] Fiocruz MS, Goncalo Moniz Inst, Salvador, BA - Brazil

^[5] SENAI CIMATEC, Hlth Technol Inst, Salvador, BA - Brazil

^[6] AC Camargo Canc Ctr, Dept Head & Neck Surg & Otorhinolaryngol, Sao Paulo - Brazil

^[7] Univ Southern Denmark, Inst Reg Hlth Res, Dept Clin Genet, Vejle Univ Hosp, Odense - Denmark

• Document type: Journal article
• Source: FRONTIERS IN ENDOCRINOLOGY; v. 11, APR 30 2020.
• Web of Science Citations: 0

Abstract

Currently, there is a lack of efficient recurrence prediction methods for papillary thyroid carcinoma (PTC). In this study, we enrolled 202 PTC patients submitted to total thyroidectomy and radioiodine therapy with long-term follow-up (median = 10.7 years). The patients were classified as having favorable clinical outcome (PTC-FCO, no disease in the follow-up) or recurrence (PTC-RE). Alterations in BRAF, RAS, RET, and TERT were investigated (n = 202) and the transcriptome of 48 PTC (>10 years of follow-up) samples was profiled. Although no mutation was associated with the recurrence risk, 68 genes were found as differentially expressed in PTC-RE compared to PTC-FCO. Pathway analysis highlighted a potential role of cancer-related pathways, including signal transduction and FoxO signaling. Among the eight selected genes evaluated by RT-qPCR, SLC2A4 and GADD45B showed down-expression exclusively in the PTC-FCO group compared to non-neoplastic tissues (NT). Increased expression of GADD45B was an independent marker of shorter disease-free survival {[}hazard ratio (HR) 2.9; 95% confidence interval (CI95) 1.2-7.0] in our cohort and with overall survival in the TCGA dataset (HR = 4.38, CI95 1.2-15.5). In conclusion, GADD45B transcript was identified as a novel prognostic marker candidate in PTC patients treated with total thyroidectomy and radioiodine therapy. (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: 15/17707-5 - Development of molecular procedures useful for differential diagnosis in thyroid nodules
• Grantee: Mateus de Camargo Barros Filho
• Support type: Scholarships in Brazil - Post-Doctorate