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

Abstract

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‐1β, IFN‐α and TGF‐β1 levels were decreased in pre‐thyroidectomy PTC patients. IFN‐α and TGF‐β1 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‐α and TGF‐β1 levels were increased in post‐thyroidectomy. Conclusion There are significant changes in the cytokine profile after surgical removal of the thyroid tumour, and IFN‐α e TGF‐β1 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.

Cytokines: Application in recurrence appraisal for differentiated thyroid carcinoma and their relation with radioiodine ablation

“…21 The possible reason it that these individuals had undergone thyroidal tumor removal and their cytokine levels did not fully recover to the levels of healthy subjects. 22 In our study, serum IL-2R was significantly associated with age ≥ 45 years during radioiodine therapy and high serum Tg concentrations. Notably, IL-2R efficiently discriminated recurrence/active status from disease-free status of patients with DTC.…”

Preoperative platelet distribution width‐to‐platelet ratio combined with serum thyroglobulin may be objective and popularizable indicators in predicting papillary thyroid carcinoma

“…Secretion of these factors by growing tumors accelerates heterogenic megakaryocytic maturation, 36 resulting in the production and secretion of immature platelets of various size into the bloodstream, thus leading to an increased PDW. Beksac et al 37 and Bertol et al 38 reported that IL‐6 levels were higher in patients with PTC than in controls, highlighting the potential role of cytokines in PTC. Yu et al 39 were the first to investigate PDW in thyroid cancer and reported that PDW was closely associated with the presence of thyroid cancer, which is inconsistent with previous studies.…”

HLA-G/sHLA-G and HLA-G-Bearing Extracellular Vesicles in Cancers: Potential Role as Biomarkers

“…In terms of diagnosis, sHLA-G is abnormally expressed in the plasma in breast ductal carcinoma ( 131 ), head and neck squamous cell carcinoma ( 129 ), gastric cancer ( 33 ), CRC ( 125 ), and papillary thyroid carcinoma ( 65 ), which is considered to be a preoperative diagnosis of cancer histopathology potential marker of aggressiveness. It is worth noting that in gastric cancer, researchers have found that sHLA-G in combination with common serum tumor markers, such as CA72-4, CA125, and CA19-1, can improve the clinical screening of gastric cancer compared with sHLA-G alone ( 132 ).…”

“…Among them, sHLA-G is derived from the secretion of sHLA-G homotypes, such as HLA-G5, HLA-G6, and HLA-G7, and the shedding of membrane-bound HLA-G homotypes, such as HLA-G1, cleaved by proteolytic hydrolysis (61). Soluble isoforms can be detected in saliva (62,63), ascitic fluid (47), plasma (26,33,48,49,56,(64)(65)(66)(67)(68)(69), thymus (70), seminal plasma (71), cerebrospinal fluid (CSF) (72,73), human first trimester and term placentas in situ and in vitro (74), and cell culture supernatant (75,76). High levels of sHLA-G are correlated with tumor histological type, lymph node metastasis, and patient survival, which can be used as a tumor marker to provide a basis for early diagnosis, differentiation, and prognosis (21).…”