Abstract
Although American Thyroid Association guidelines offer a risk stratification scheme for thyroid cancer patients, there is a continuous need for more sophisticated biomarkers that can predict disease progression. In this study, we aim to evaluate the prognostic value of class III beta-tubulin (TUBB3) and uncover the relationship between TUBB3 and invasive potential in thyroid carcinoma. Immunohistochemistry (IHC) for TUBB3 and E-cadherin was performed on a total of 254 cases of thyroid cancer specimens. Tumor budding at the invasive margin was evaluated. In vitro functional studies were also performed; the protein and mRNA levels of TUBB3 were compared among the five cell types at baseline, with transwell invasion and after blocking of TUBB3 by shRNA. IHC revealed that the levels of TUBB3 were higher in conventional papillary carcinomas (cPTCs) and anaplastic thyroid carcinomas (ATCs). In univariate analysis, high tumor budding and TUBB3 expression were associated with inferior progression-free survival in cPTC. The results of a Western blot and RT-PCR agreed with the IHC finding. The results were further validated through data from The Cancer Genome Atlas database. Our results suggest that high expression of TUBB3 in thyroid carcinoma could predict invasive potential and possibly be linked with epithelial–mesenchymal transition.
Highlights
Thyroid cancer is one of the most common human malignancies with a steadily rising incidence worldwide
The 2015 American Thyroid Association (ATA) guidelines proposed an updated risk stratification system modified from the 3-tiered 2009 system, combining additional factors that include the extent of lymph node involvement and mutational status [15,16]
We comprehensively investigated the expression of TUBB3 in various types of thyroid carcinomas, including the newly emerging entity “noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)”
Summary
Thyroid cancer is one of the most common human malignancies with a steadily rising incidence worldwide. Despite a 5-year survival rate of nearly 100%, a minority of papillary carcinomas (PTCs), including aggressive histologic variants and even PMCs, may develop distant metastasis or local recurrence during the follow-up period, which severely affects patients’ quality of life [6,7,8,9,10]. This implies a biologic diversity of thyroid carcinoma, requiring more precise stratification to identify the subgroup that needs aggressive management and meticulous study. We aim to evaluate the clinicopathologic significance of TUBB3 and its potential role as a therapeutic target in thyroid carcinoma
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