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

Abstract

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 TBX22 in PTC. Comprehensive analyses of TBX22 were based on the public databases and our local qRT-PCR cohort. We observed that TBX22 was significantly downregulated in PTC compared with normal tissues. TBX22 was associated with several clinicopathological factors in PTC. Low TBX22 expression correlated with BRAFV600E and TERT mutation. Functional enrichment analysis revealed that cancer-related pathways and immune progress were closely associated with TBX22 in PTC. In TBX22-low PTC, high immune infiltration levels with increased CD8+ T cells, natural killer, M1 macrophages, and T-regulatory cells were observed. TBX22 was negatively correlated with the activity of different steps of the anticancer immunity cycle. Functionally, overexpression of TBX22 inhibited the proliferation, invasion, and migration in PTC cells, while knocking down of TBX22 showed the opposite effects. The present findings disclose that TBX22, as an immune microenvironment-related biomarker, could be an important tumor suppresser gene and might inform the management of PTC patients better.

BRAF-activated WT1 contributes to cancer growth and regulates autophagy and apoptosis in papillary thyroid carcinoma

“…In recent years, with the development of high-throughput detection techniques, it has become more convenient to identify promising biomarkers to predict the prognosis and recurrence of various malignancies [ 4 – 6 ]. Based on these techniques, the measurement of gene mutation status, including BRAF, RAS and TERT mutations, also serves as an effective method for exploring regulatory mechanisms and provides a strategy for the individualized treatment of PTC in patients [ 7 – 9 ]. BRAF mutation is the most common genetic lesion in PTC, accounting for 50% of all cases, and the BRAF V600E mutation is the most frequent mutation (95%) among all mutation types [ 10 ].…”

The ETNK2 gene promotes progression of papillary thyroid carcinoma through the HIPPO pathway

“…With the improvement of diagnostic technology, the incidence of thyroid cancer (TC) has increased significantly [1][2][3][4][5], and papillary thyroid carcinoma (PTC) is the most common pathological subtype of thyroid cancer [2,[6][7][8][9]. The prognosis of PTC patients is usually relatively good [7].…”

Aberrant expression of PROS1 correlates with human papillary thyroid cancer progression

“…Though the complex mechanism leading to PTC remains unclear, the critical role of genetic alteration in PTC biology has been proved in recent years, such as B-type RAF kinase ( BRAF V600E ), telomerase reverse transcriptase ( TERT ), tumor protein P53 ( TP53 ), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA ) ( Dong et al, 2020 ; Prete et al, 2020 ; Ricarte-Filho et al, 2009 ; Vitale et al, 2017 ; Xing et al, 2014 ), and so on. BRAF V600E represents the most common mutation in PTC ( Kim et al, 2010 ).…”