Plasma levels of soluble HLA-G and cytokines in papillary thyroid carcinoma before and after thyroidectomy

Background Increasing evidence shows that chronic inflammation plays an important role in thyroid tumorigenesis. Cytokines as central mediators in inflammatory microenvironment can present both pro-tumour and anti-tumour effects and cytokine release may be influenced by soluble HLA-G (sHLA-G), an immune checkpoint molecule whose expression can also be induced by certain cytokines. Aim To understand the role of these soluble factors in papillary thyroid cancer (PTC). Methods We evaluated plasma levels of sHLA-G and of 13 cytokines using ELISA and flow cytometry, respectively, in PTC patients at two time points: pre- and post-thyroidectomy; and control subjects. Results Compared with controls, IL-6 levels were increased, while IL-1 beta, IFN-alpha and TGF-beta 1 levels were decreased in pre-thyroidectomy PTC patients. IFN-alpha and TGF-beta 1 efficiently discriminated patients from controls and were associated with extrathyroidal extension and lymph node metastasis, respectively. In addition, TNF and IL-13 were associated with male gender, lymph node metastasis and Hashimoto thyroiditis, and sHLA-G with tumour invasion. Compared with pre-thyroidectomy, IL-4, IL-10, TNF, IFN-alpha and TGF-beta 1 levels were increased in post-thyroidectomy. Conclusion There are significant changes in the cytokine profile after surgical removal of the thyroid tumour, and IFN-alpha e TGF-beta 1 showed to be promising cytokines for discriminating PTC patients from controls. We also found that different cytokines are associated with clinicohistopathological characteristics of PTC related to poor prognosis, suggesting that cytokines seem to play an important role in PTC development and management.