Expression Of High Mobility Group Box1, Matrix Metalloproteinase-9and Vascular Endothelial Growth Factor-C And Its Significance In Thyroid Carcinoma

Background and objectiveThyroid carcinoma is one of common malignant tumors and thyroid tumors with5%-10%are thyroid carcinomas, women have a higher prevalence. Differentiated thyroid carcinomas have accounted for90%of thyroid carcinoma, including papillary thyroid carcinoma and follicular thyroid carcinoma which both are derived from thyroid follicular cells, undifferentiated carcinoma is relatively rare, in addition, there also includes medullary thyroid carcinoma which is derived from the thyroid parafollicular cells.The different histological types of thyroid cancer are, the degree of malignancy and metastasis is not the same, but all have the character of strong invasiveness and being easy to metastasize. Papillary thyroid carcinoma is easy to metastasize in the lymph node, whereas follicular thyroid carcinoma is main to spreading with hematogenous metastasis. The prognosis of thyroid patient is closely related with invasion and metastasis of cancer cells. So, it is in favour of early diagnosis, differential diagnosis and choosing therapeutic schedule by detecting markers of malignant thyroid tumor with the ability of tumor invasion and metastasis.High mobility group box1is a nuclear non-histone protein, its levels are reported in a variety of tumor types now, the expression of HMGB1is closely with tumor invasiveness and metastasis. The molecular mass of matrix metalloproteinase-9is closely related with the invasiveness and metastasis of malignant tumor. The mechanism may is HMGB1in interior of larger tumors may effect on fibrinolysis system by releasing to surrounding environment from the necrotic tumor cells, thus the basilar membrane and extracellular matrix is destroyed.VEGF-C secreted from tumor cells by the way of autocrine and paracrine that can promote tumor matastasize by inducing the formation of tumor lymph vessel. MAPK and NF-kB may activated by HMGB1have relationship with the expression of VEGF-C and MMP-9, that has been proved in partly tumors.The researche about the interaction during HMGB1and MMP-9, VEGF-C in thyroid carcinoma have not been reported. The purpose of this study is to investigate the expression of HMGB1, MMP-9and VEGF-C in thyroid carcinoma and their potential correlations, having provided experimental and theoretical basis for the diagnosis, treatment and prognosis of thyroid carcinoma.Methods1. Detected the expression of HMGB1, MMP-9, VEGF-C protein and HMGB1mRNA in thyroid specimens which exsected from The First Alliliated Hospital of Zhengzhou University between January2008and December2010and pathological confirmed by the technology of immunohistochemistry (SP) and in situ hybridization. The specimens include96cases of thyroid carcinoma tissues (58cases of papillary thyroid carcinoma tissues,20cases of follicular thyroid carcinoma tissues,18cases of medullary thyroid carcinoma tissues) and55cases of thyroid non-carcinoma tissues (20cases of thyroid adenoma tissues,25cases of nodular goiter tissues and10cases of normal thyroid tissues).2. Statistical analysis:All the datas had been 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 text level of significant difference is a=0.05. Results1. The positive rate of HMGB1protein was68.75%(66/96) in thyroid carcinoma tissues,30.00%(6/20) in thyroid adenoma tissues,20.00%(5/25) in nodular goiter tissues and there was no expression in normal thyroid tissues. The expression of HMGB1protein in thyroid carcinoma tissues was significantly higher than that in thyroid non-carcinoma, the difference was statistically significantly (P<0.05), the comparison between any two groups of the three non-carcinoma tissues was no statistically significantly (P>0.05). The expression of HMGB1protein in follicular thyroid carcinoma tissues was higher than that in papillary thyroid carcinoma tissues and medullary thyroid carcinoma tissues, the positive rates were75.00%(15/20),72.41%(42/58) and50.00%(9/18), the comparisons between the former group and the latter groups were no statistically significantly (P>0.05). The expression of HMGB1protein was gradually increased with bigger of carcinoma volume, the positive rate was76.19%(48/63) in the group with tumor diameter≥1.0cm and54.55%(18/33) in the group with tumor diameter<1.0cm, the difference was statistically significantly (P<0.05). The expression of HMGB1had closely correlation with metastasis of lymph node, the positive rates were79.59%(39/49) and57.45%(27/47) respectively in the group with lymph node metastasis and the group without lymph node metastasis, the difference was statistically significantly (P<0.05). The positive rate of HMGB1protein was60.71%(17/28) in the male group and72.06%(49/68) in the female group, the difference was no statistically significantly (P>0.05). The positive rate of HMGB1protein was72.22%(39/54) in the group with age≥45yeas and64.29%(27/42) in the group with age<45years, the difference was no statistically significantly (P>0.05), so, the expression of HMGB1protein had no association with thyroid carcinoma patients’sex and age.2. The positive rate of MMP-9protein was66.67%(64/96) in thyroid carcinoma tissues,35.00%(7/20) in thyroid adenoma tissues,32.00%(8/25) in nodular goiter tissues and20.00%(2/10) in normal thyroid tissues. The expression of MMP-9protein in thyroid carcinoma tissues was significantly higher than that in thyroid non-carcinoma, the difference was statistically significantly (P<0.05), the comparison between any two groups of the three non-carcinoma tissues was no statistically significantly (P>0.05). The expression of MMP-9protein in follicular thyroid carcinoma tissues was significantly higher than that in papillary thyroid carcinoma tissues and medullary thyroid carcinoma tissues, the positive rates were90.00%(18/20),62.07%(36/58) and55.56%(10/18), the comparisons between the former group and the latter groups were statistically significantly (P<0.05). The expression of MMP-9protein was gradually increased with bigger of carcinoma volume, the positive rate was74.60%(47/63) in the group with tumor diameter≥1.0cm and51.52%(17/33) in the group with tumor diameter<1.0cm, the difference was statistically significantly (F<0.05). The expression of MMP-9had closely correlation with lymph node metastasis, the positive rates were77.55%(38/49) and55.32%(26/47) respectively in the group with lymph node metastasis and the group without lymph node metastasis, the difference was statistically significantly (P <0.05). The positive rate of MMP-9protein was64.29%(18/28) in the male group and67.65%(46/68) in the female group, the difference was no statistically significantly (P>0.05). The positive rate of MMP-9protein was66.67%(36/54) in the group with age≥45yeas and66.67%(28/42) in the group with age<45years, the difference was no statistically significantly (P>0.05), so, the expression of MMP-9protein had no association with thyroid carcinoma patients’sex and age.3. The positive rate of VEGF-C protein was69.79%(67/96) in thyroid carcinoma tissues,15.00%(3/20) in thyroid adenoma tissues,12.00%(3/25) in nodular goiter tissues and10.00%(1/10) in normal thyroid tissues. The expression of VEGF-C protein in thyroid carcinoma tissues was significantly higher than that in thyroid non-carcinoma, the difference was statistically significantly (P<0.05), the comparison between any two groups of the three non-carcinoma tissues was no statistically significantly (P>0.05). The expression of VEGF-C protein in papillary thyroid carcinoma tissues was significantly higher than that in follicular thyroid carcinoma tissues and medullary thyroid carcinoma tissues, the positive rates were81.03%(47/58),55.00%(11/20) and50.00%(9/18), the comparisons between the former group and the latter groups were statistically significantly (P<0.05). The expression of VEGF-C had closely correlation with lymph node metastasis, the positive rates were79.59%(39/49) and59.57%(28/47) respectively in the group with lymph node metastasis and the group without lymph node metastasis, the difference was statistically significantly (P<0.05). The positive rate of VEGF-C protein was74.60%(47/63) in the group with tumor diameter≥1.0cm and60.61%(20/33) in the group with tumor diameter<1.0cm, the difference was no statistically significantly (P>0.05). The positive rate of VEGF-C protein was71.43%(20/28) in the male group and69.12%(47/68) in the female group, the difference was no statistically significantly (P>0.05). The positive rate of VEGF-C protein was74.07%(40/54) in the group with age≥45yeas and64.29%(27/42) in the group with age <45years, the difference was no statistically significantly (P>0.05), so, the expression of VEGF-C protein had no association with thyroid carcinoma patients’ sex, age and the diameter of carcinoma.4. The positive rate of HMGB1mRNA was52.08%(50/96) in thyroid carcinoma tissues,10.00%(2/20) in thyroid adenoma tissues,8.00%(2/25) in nodular goiter tissues and there was no expression in normal thyroid tissues. The expression of HMGB1mRNA in thyroid carcinoma tissues was significantly higher than that in thyroid non-carcinoma, the difference was statistically significantly (P<0.05), the comparison between any two groups of the three non-carcinoma tissues was no statistically significantly (P>0.05). The expression of HMGB1mRNA in follicular thyroid carcinoma tissues was higher than that in papillary thyroid carcinoma tissues and medullary thyroid carcinoma tissues, the positive rates were60.00%(12/20),53.45%(31/58) and38.89%(7/18), the comparisons between the former group and the latter groups were no statistically significantly (P>0.05). The expression of HMGB1mRNA was gradually increased with the bigger of carcinoma volume, the positive rate was60.32%(38/63) in the group with tumor diameter≥1.0cm and36.36%(12/33) in the group with tumor diameter<1.0cm, the difference was statistically significantly (P<0.05). The expression of HMGB1had closely correlation with lymph node metastasis, the positive rates were63.27%(31/49) and40.43%(19/47) respectively in the group with lymph node metastasis and the group without lymph node metastasis, the difference was statistically significantly (P<0.05). The positive rate of HMGB1mRNA was42.86%(12/28) in the male group and55.88%(38/68) in the female group, the difference was no statistically significantly (P>0.05). The positive rate of HMGB1mRNA was55.56%(30/54) in the group with age≥45yeas and47.62%(20/42) in the group with age<45years, the difference was no statistically significantly (P>0.05), so, the expression of HMGB1mRNA had no association with thyroid carcinoma patients’sex and age.5. In thyroid carcinoma tissues, there was a positive correlation between the expression of HMGB1protein and HMGB1mRNA (r=0.253, P<0.05); there was a positive correlation between the expression of HMGB1protein and MMP-9protein (r=0.238, P<0.05); there was a positive correlation between the expression of HMGB1protein and VEGF-C protein (r=0.242, P<0.05); there was a positive correlation between the expression of MMP-9protein and VEGF-C protein (r=0.209, P<0.05).Conclusions1. HMGB1、MMP-9、VEGF-C may be involved in the occurrence and development of thyroid carcinoma; VEGF-C may be involved in the metastasis of thyroid carcinoma.2. There was a positive correlation during the expression of HMGB1, MMP-9and VEGF-C, it suggests that they may have played synergistic effect in the occurrence, progression and invasion, metastasis of thyroid carcinoma.3. The expressions of HMGB1protein and HMGB1mRNA are both higher in thyroid carcinoma, it indicates that regulation of HMGB1expression occurred in the transcription stage.