Expression Of SOCS3 In Thyroid Carcinoma And Its Clinical Significance

The morbidity of malignant tumors is increasing gradually in recent years. However, the molecular mechanisms for the development of malignant tumors have not been well characterized,which are always the study hotspots in bio-medical domain. One of the research highlights is the activation of intracellular signal transduction cascades such as the JAK-STAT pathway on tumor formation. STAT3 is known to act as an oncogene in most malignancies and play a critical role in regulating cellular growth,proliferation and differentiation. It may prevent tumor cell death, stimulate expression of angiogenic factors and induce expression of extracellular matrix degradation enzymes thus resulting in enhanced metastatic potential. Suppressors of cytokine signaling (SOCS)-3 belongs to the SOCS family, which inhibit various cytokine-mediated pathways, in particular the JAK/STAT3 signalling. SOCS proteins are believed to be negative feedback loop regulators of cytokine-mediated signaling pathways by reducing phosphorylation of JAKs or STATs,STAT dimerization or import to the nucleus etc. Intensive study demonstrated that the expression of SOCS genes has been proved to be lost in several malignant diseases, such as lung cancer, head-neck squamous cell carcinoma,hepatocarcinoma, ovarian cancer and T-cell lymphoma. Reports also identified that the transcription silencing is closely related to the frequent hypermethylation in CpG islands of the functional SOCS3 promoter. By contrast, levels of SOCS3 on prostate cancer and breast cancer were revealed to be elevated and contribute to growth advantage and higher malignant phenotype. It is well accepted that hormone plays an essential role in the development and progression of prostate cancer and breast cancer. Consistent with this notion, recent studies have shown that androgen is capable of up-regulating SOCS3 protein levels in prostate cancer and the elevation of SOCS gene expression might be part of the host/tumor response or a response to autocrine/paracrine growth hormone and prolactin in breast cancer.The pathogenesis of thyroid carcinoma is not fully understood. Results indicated that hormone implicated a likely mechanism for thyroid oncogenesis in analogy with prostate cancer and breast cancer. However,what has not been delineated is the expression of SOCS3 in thyroid carcinoma and its clinical significance.Objective: To investigate the expression of SOCS3 protein in thyroid carcinoma, thyroid adenoma and normal thyroid tissue and its revelant clinic pathological characteristics,and to explore the relationships between SOCS3 and STAT3, P-STAT3, VEGF and Bcl-2 in JAK/STAT pathway. Our findings may set up the experimental foundation for research on the pathogenesis and provide a new idea for clinical therapy of thyroid carcinoma.Method: SP immunohistochemistry was used to detect the expression of SOCS3, STAT3, P-STAT3, VEGF and Bcl-2 in 70 cases of thyroid carcinomas (including 36 papillary, 18 follicular,12 medullary and 4 anaplastic carcinomas), 30 cases of thyroid adenoma and 12 cases of normal thyroid tissue. The correlation analyses of SOCS3 with the other four relevant factors,are made with reference to clinical pathologic parameters of thyroid carcinomas.Results: (1)Comparison of expressions of SOCS3, STAT3, P-STAT3, VEGF and Bcl-2 in thyroid carcinoma,adenoma and normal thyroid tissue were carried out seperately. The results demonstrated that all of the factors above showed higher expression in thyroid carcinoma than in the other groups. The differences were statistically significant (p <0.01, p <0.01, p <0.01, p <0.05, p <0.01).(2)The expression of SOCS3 was positively related to histological type and cervical lymph node metastasis ( p <0.05,P<0.01),but was not statistically correlated with age and gender. (all p >0.05) (3)The expression of STAT-3, P-STAT3, VEGF and Bcl-2 was positively related to the expression of SOCS3 in thyroid carcinoma tissues (all p <0.01).Conclusion: High expression of SOCS3 in thyroid carcinoma was testified and positively related to the expression of STAT3, p -STAT3, VEGF and Bcl-2 in JAK/STAT pathway. This shows that the expression of SOCS3 may be regulated by multi-factors in the signal transduction pathway,which is closely related to the pathogenesis of thyroid carcinoma.