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.
Highlights
The incidence of thyroid carcinoma has tripled over the last 35 years, affecting more than 560,000 people worldwide in 2018 [1]
We investigated the most common gene alterations described in papillary thyroid carcinoma (PTC), as well as transcriptomic data, to identify markers able to anticipate the outcome of patients treated with total thyroidectomy followed by radioiodine therapy
Patients with a minimum follow-up of 10 years were included in the large-scale gene expression analysis, while specific mutations/rearrangements and mRNAs levels were evaluated in patients followed for at least 5 years
Summary
The incidence of thyroid carcinoma has tripled over the last 35 years, affecting more than 560,000 people worldwide in 2018 [1]. Papillary thyroid carcinoma (PTC) represents 80–85% of all thyroid cancer, presenting a high cure rate and a 5-years overall survival of 98% [2]. Clinical-pathological features, such as distant and lymph node metastasis, extrathyroidal extension, and tall cell histologic variant, are associated with more aggressive PTC [5]. Low-risk PTC may be eligible for minimalistic surgical approaches (such as thyroid lobectomy) or active surveillance. A more aggressive intervention (such as total thyroidectomy, prophylactic neck dissection, or radioiodine therapy) could be reserved for high risk PTC [5]
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