AVALIAÇÃO DO HLA-G SOLÚVEL E DO PERFIL DE CITOCINAS COMO POTENCIAIS BIOMARCADORES PLASMÁTICOS DO CARCINOMA PAPILÍFERO DA TIREOIDE
Papillary thyroid carcinoma; biomarkers; soluble HLA-G; cytokines; inflammation;
Papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Limitations in diagnosis and prognosis determination still represent a great challenge for clinical management of CPT. Thus, the search for new targets for minimally invasive diagnosis became crucial. Considering the recognized association between CPT and chronic inflammation, the aim of the present study was to investigate the role of plasma cytokines and soluble HLA-G as potential biomarkers for CPT. Plasma of PTC patients was obtained before (n = 85) and after thyroidectomy (n = 77). Plasma levels of 13 cytokines were measured by flow cytometry bead-based multiplex and single-plex assays, and soluble HLA-G was measured by enzyme-linked immunosorbent assay (ELISA). The results were compared to each other, to healthy control subjects (n = 80). The association of these molecules in plasma with clinicopathological features and the type of response to treatment presented in patients was also investigated. Levels of IL-4, IL-10, TNF, IFN-α and TGF-β1 were significantly higher in post-thyroidectomy plasma compared to pre-thyroidectomy. In comparison to controls, a pattern of differentially concentrated cytokines was observed in both pre-thyroidectomy and post-thyroidectomy plasma. IFN-α and TGF-β1 were able to independently discriminate PTC patients from controls, and IFN-α presented the best diagnostic performance. Increase in IL-1β and decrease in IL-12p70 plasma levels was independently associated with larger tumors (> 2.0 cm), while decreased sHLA-G levels was independently associated with the presence of invasion. Patients presenting biochemical/structural incomplete response presented higher levels of IL-5 and IFN-α when compared to patients with excellent/indeterminate response. In conclusion, our findings show a significant change in plasma cytokine profile after surgical removal of thyroid tumor and the potential of plasma IFN-α and TGF-β levels to discriminate PTC patients from controls. Risk factors for worse prognosis were also associated with differential expression of cytokines. Overall, these data corroborate the influence of inflammatory response on the development of CPT.