Association of HLA-G, BRAF and TERT genes with malignancy of papillary thyroid carcinoma

Abstract

The thyroid carcinoma is the most common malignancy of the endocrine system, and papillary thyroid carcinoma (PTC) corresponds to 80% of cases of differentiated carcinoma type. Somatic mutations have been associated with PTC, as the mutations of BRAF and TERT genes, associated with poor prognosis of the disease. Besides BRAF and TERT, other molecules have been related with poor prognosis when expressed in tumor cells, such as HLA-G molecule, particularly as it inhibits antitumor immune cells (CD8 + cytotoxic T cells and natural killer cells). Despite the evidence of HLA-G expression in patients with PTC, little is known about the role and the mechanisms of regulation of HLA-G, BRAF and TERT genes in the disease. In this context, microRNAs (miRNA) are very important in post-transcriptional regulation of genes and several miRNAs are induced in the PTC. Therefore, we aimed to study patients with PTC evaluating: i) expression of HLA-G and BRAF in thyroid tissue and plasma levels of sHLA-G, ii) polymorphisms throughout the HLA-G gene and the presence of the T1799A mutation of gene BRAF and C228T e C250T mutations of TERT gene and iii) detection of miRNAs that might be regulating the BRAF, HLA-G and TERT genes. Achieved the goals, we might be able to: i) relate the variability of the HLA-G gene, the presence BRAF and TERT mutations and the expression of BRAF and HLA-G molecules with the prognosis of patients with PTC, ii) search for possible miRNAs that could modulate the expression of these genes in the PTC, and iii) evaluate the morbidity of the presence of these factors in patients with PTC. Thus, knowledge of the role of HLA-G, BRAF and TERT genes in PTC and its regulatory mechanisms can help to identify new biomarkers and the development of new therapeutic approaches, improving existing treatments as well as aiding in the early diagnosis of PTC.