| Background and objective:Thyroid carcinoma is the most common malignant tumor in the endocrine system, which accounts for more than90%. Thyroid carcinoma is also one of the fastest-growing malignant tumors in recent years. According to the histopathological classification, thyroid carcinoma contains papillary thyroid carcinoma, follicular thyroid carcinoma, undifferentiated thyroid carcinoma and medullary thyroid carcinoma. There are many different histological types in the thyroid cancer, and their prognosis and the rules of development are not all the same. So, it is necessary for early diagnosis. There are a lot of diagnostic methods, including the most important light microscope, but it still has some difficulties for identifying the atypical thyroid carcinomas and the thyroid microcarcinomas. Because of this, molecular biotechnologies emerge to help. It chooses therapeutic schedules by detecting markers of malignant tumor with high abilities of invasion and metastasis. Also, it provides an important basis for tumor molecular diagnosis.High mobility group box1was found in the bovine thymus40years ago. This protein has higher electrophoretic mobility, therefore it is named high mobility group protein. HMGB1is a nuclear binding protein, and plays an important role in DNA recombination, DNA repair, DNA replication and genetic transcription. It has found that the expression of HMGB1is closely related with tumor formation, invasiveness and metastasis, especially with gastric cancer, colorectal cancer, and pancreatic cancer. The pro-inflammation effect of HMGB1works through two major signal pathways, one of which is Ras, MAPK signaling pathway. It phosphorylates the MAPKs and activates NF-κB, then induces the inflammation and the migration of immune cells. In the other signal pathway it activates Cdc42and Rac, and leads to the reconstruction of cytoskeleton, then regulates the growth of axons in the growth and development of the neurons. The mechanism between tumor development and HMGB1was not entirely clear, but it may be related to these two signal pathways above.NF-κB is one of nuclear transcription factors, which is found in eukaryotic cells and controls the transcription of DNA. NF-κB combines with particular nucleotide sequence of HTT gene-linked polymorphic region and initiates gene transcription. It plays an important role in the life process such as cell proliferation, cell differentiation, tumor formation and metastasis. It has been proved NF-κB associates with many kinds of tumors, such as pancreatic cancer and esophageal cancer. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimulus such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection (κ light chains are critical components of immunoglobulins). Incorrect regulation of NF-κB has been proved to link to cancer, inflammatory and autoimmune diseases, septic shock, and viral infection. NF-κB has also been implicated in processes of synaptic plasticity and memory. In mammals, the family members of NF-κB have five sub-units, two most important of which are p50and p65. P50locates in the DNA binding domain. P65could enhance the activity of transcription through Rel homology domain and promote the connection of p50and DNA.The researches about the interaction between HMGB1and NF-κB p50, NF-κB p65in thyroid carcinoma have not been reported. To further explore the relationship between these three indicators, the study detects the expressions of HMGB1, NF-κB p50, NF-κB p65proteins by immunohistochemistry in100cases of thyroid carcinoma and60cases of non-cancerous tissues. The aim is to clarify the relationships between the expressions of HMGB1, NF-κB p50, NF-κB p65and the occurrence, development and metastasis of thyroid carcinoma, and to provide experimental basis for the diagnosis of thyroid carcinoma.Methods:1. Detected the expressions of HMGB1, NF-κB p50, NF-κB p65proteins in58cases of papillary thyroid carcinoma tissues,20cases of follicular thyroid carcinoma tissues,22cases of medullary thyroid carcinoma tissues,20cases of thyroid adenoma tissues,20cases of nodular goiter tissues and20cases of normal thyroid tissues by the technology of immunohistochemistry (SP).2. Statistical analysis:All data was analyzed by SPSS17.0statistical software package. The Chi-square was used for the comparison of positive rates; the Spearman’s correlation analysis was used for analyzing the correlation of two variables. The level of significant difference was a=0.05. Results:1. The positive rates of HMGB1protein in thyroid carcinoma, thyroid adenoma,nodular goiter and normal thyroid tissues were70.00%(70/100),30.00%(6/20),25.00%(5/20),10.00%(2/20) respectively. The expression of HMGB1protein in thyroid carcinoma tissues was not related to patients’ sex, age or tumor tissue types(P>0.05), but had association with tumor diameter and lymph node metastasis(P<0.05).2. The positive rates of NF-κB p50protein in thyroid carcinoma, thyroidadenoma, nodular goiter and normal thyroid tissues were72.00%(72/100),35.00%(7/20),30.00%(6/20),10.00%(2/20) respectively. The expression of NF-κB p50protein in thyroid carcinoma tissues was not related to patients’ sex,age or tumor tissue types(P>0.05), but had association with tumor diameter and lymph node metastasis(P<0.05).3. The positive rates of NF-κB p65protein in thyroid carcinoma, thyroid adenoma, nodular goiter and normal thyroid tissues were89.00%(89/100),40.00%(8/20),35.00%(7/20),15.00%(3/20) respectively. The expression of NF-κB p65protein in thyroid carcinoma tissues was not related to patients’ sex, age or tumor’ tissue types(P>0.05), but had association with tumor diameter and lymph node metastasis(P<0.05).4. In thyroid carcinoma tissues, there were positive correlations between any two proteins. The expression of HMGB1protein positively correlated with NF-κB p50protein (r=0.467, P<0.05) and NF-κB p65protein (r=0.398, P<0.05) respectively; NF-κB p50protein expression and NF-κB p65protein expression were also positively correlated (r=0.350, P<0.05).Conclusions:1. The positive expression rates of HMGB1, NF-κB p50and NF-κB p65proteins in normal thyroid, nodular goiter, thyroid adenoma, thyroid carcinoma tissues revealed a gradual increasing trend. And the expressions of HMGB1, NF-κB p50and NF-κB p65proteins in thyroid carcinoma tissues were significantly higher than that in non-cancerous tissues. It suggests that HMGB1, NF-κB p50and NF-κB p65proteins may be involved in the occurrence of thyroid carcinoma.2. The positive expression rates of HMGB1, NF-κB p50and NF-κB p65proteins gradually increased with the larger thyroid carcinoma size and lymph node metastasis. It indicates that the high expressions of HMGB1, NF-κB p50and NF-κB p65proteins may be related with the development of thyroid carcinoma and further lymph node metastasis.3. HMGB1, NF-κB p50, NF-κB p65proteins were all highly expressed in thyroid carcinoma, and they were positively correlated between any two of them. It suggests that HMGB1, NF-κB p50, NF-κB p65proteins may play a synergistic effect in the occurrence, development and lymph node metastasis of thyroid carcinoma. |
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