AUTHOR=Dong Xubin , Song Jingjing , Hu Jing , Zheng Cheng , Zhang Xiaohua , Liu Haiguang 

TITLE=T-Box Transcription Factor 22 Is an Immune Microenvironment-Related Biomarker Associated With the BRAFV600E Mutation in Papillary Thyroid Carcinoma

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.590898

DOI=10.3389/fcell.2020.590898

ISSN=2296-634X

ABSTRACT=<p>Papillary thyroid cancer (PTC) is the most common malignant disease in endocrine systems. T-box transcription factor 22 (TBX22) is a phylogenetically conserved family member that has not been widely characterized in cancers. In this study, we explored the potential clinical significance and biological functions of <italic>TBX22</italic> in PTC. Comprehensive analyses of <italic>TBX22</italic> were based on the public databases and our local qRT-PCR cohort. We observed that <italic>TBX22</italic> was significantly downregulated in PTC compared with normal tissues. <italic>TBX22</italic> was associated with several clinicopathological factors in PTC. Low <italic>TBX22</italic> expression correlated with <italic>BRAF</italic><sup><italic>V</italic>600<italic>E</italic></sup> and TERT mutation. Functional enrichment analysis revealed that cancer-related pathways and immune progress were closely associated with <italic>TBX22</italic> in PTC. In TBX22-low PTC, high immune infiltration levels with increased CD8<sup>+</sup> T cells, natural killer, M1 macrophages, and T-regulatory cells were observed. <italic>TBX22</italic> was negatively correlated with the activity of different steps of the anticancer immunity cycle. Functionally, overexpression of <italic>TBX22</italic> inhibited the proliferation, invasion, and migration in PTC cells, while knocking down of <italic>TBX22</italic> showed the opposite effects. The present findings disclose that <italic>TBX22</italic>, as an immune microenvironment-related biomarker, could be an important tumor suppresser gene and might inform the management of PTC patients better.</p>