Avaliação do HLA-G solúvel e do perfil de citocinas como potenciais biomarcadores plasmáticos do carcinoma papilífero da tireoide

Abstract

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 PTC. Thus, the search for new targets for minimally invasive diagnosis became crucial. Considering the recognized association between PTC and chronic inflammation, the aim of the present study was to investigate plasma levels of cytokines and soluble HLA-G as potential biomarkers for diagnosis and/or prognosis of CPT. We studied PTC patients before (n = 85) and after thyroidectomy (n = 77), and 80 controls. Plasma levels of 13 cytokines were measured by flow cytometry beadbased assays, and soluble HLA-G was measured by ELISA. Data were evaluated using univariate and multivariate analyses, and ROC curves. Compared to prethyroidectomy, IL-4, IL-10, TNF, IFN-α and TGF-β1 levels were increased in postthyroidectomy. Compared to controls: i) sHLA-G levels were decreased after thyroidectomy, ii) IL-6 levels were increased, while IL-1β, IFN-α and TGF-β1 levels were decreased in pre-thyroidectomy, iii) IL-5 and IL-6 levels were increased, while IFN-α and TGF-β1 were decreased in post-thyroidectomy. IFN-α and TGF-β1 discriminated patients from controls after multiple logistic regression analysis, and IFNα presented the best diagnostic performance. Increased IL-1β and decreased IL-12p70 levels presented independent associations with larger tumors (>2.0 cm), while decreased sHLA-G levels were associated with invasion. Patients presenting biochemical/structural incomplete response presented higher IL-5 and IFN-α levels when compared to patients with excellent/indeterminate response. In conclusion, a differential cytokine profile was observed in plasma before and after thyroidectomy, and IFN-α and TGF-β1 levels seems to be potential biomarkers candidates for PTC diagnosis. Cytokines were associated with factors of poor prognosis (IL-1β e IL-12p70) and unsatisfactory response to treatment (IFN-α e IL-5). However, further studies are needed to confirm the clinical relevance of these molecules for PTC.