BRAFV600E突变对甲状腺乳头状癌HMGB1及MMP-9表达的影响

目的探究BRAF^V600E突变对甲状腺乳头状癌(PTC)高迁移率族蛋白1(HMGB1)及基质金属蛋白酶-9(MMP-9)表达的影响。方法选取2018年1月至2019年11月在本院行甲状腺全切除术或次全切除术的116例PTC患者及匹配癌组织标本作为PTC组,另择同时期体检正常的30例健康人作为对照组。检测PTC患者BRAFV600E基因类型,免疫组化法及Western blot法检测PTC患者甲状腺癌组织中HMGB1、MMP-9表达情况,酶联免疫吸附法检测受试者血清HMGB1、MMP-9水平,并收集PTC患者临床资料。结果 116例PCT患者检出59例BRAF^V600E突变型、57例为BRAFV600E野生型,PTC患者BRAF^V600E突变型为50.86%(59/116)。免疫组化法分析结果显示BRAFV600E突变型HMGB1、MMP-9阳性表达率均显著高于BRAFV600E野生型,差异有统计学意义(P<0.05);Western blot法检测结果显示BRAFV600E突变型HMGB1表达量、MMP-9表达量显著高于BRAF^V600E野生型,差异有统计学意义(P<0.05)。PTC组BRAF^V600E突变型及BRAF^V600E野生型血清HMGB1、MMP-9水平均显著高于对照组,差异有统计学意义(P<0.05),PTC患者BRAFV600E突变型与BRAF^V600E野生型在血清HMGB1、MMP-9水平上比较,差异无统计学意义(P>0.05)。BRAF^V600E突变型TNM分期Ⅲ~Ⅳ期、包膜浸润、多发病灶、淋巴结转移占比显著高于BRAF^V600E野生型,差异有统计学意义(P<0.05)。二元Logistic结果显示,合并包膜浸润、多发病灶、组织HMGB1阳性、组织MMP-9阳性均是BRAF^V600E突变型的影响因素(P<0.05)。结论 PTC患者BRAF^V600E突变型组织HMGB1、MMP-9阳性表达率显著高于BRAF^V600E野生型,且组织HMGB1阳性、MMP-9阳性是BRAF^V600E突变型的影响因素。

Effect of BRAF mutation on the expression of HMGB1 and MMP-9 in papillary thyroid carcinoma

Objective To explore the effect of BRAF^V600Emutation on the expression of HMGB1 and MMP-9 in papillary thyroid carcinoma(PTC). Methods A total of 116 PTC patients who underwent total or subtotal resection in our hospital from January 2018 to November 2019 and matched cancer tissue samples were selected as study objects,and another 30 healthy patients who underwent normal physical examination during the same period were selected as the control group. The BRAFV600Egene types of PTC patients were detected,the expressions of HMGB1 and MMP-9 in thyroid tissues of PTC patients were detected by immunohistochemistry and Western blot,the serum levels of HMGB1 and MMP-9 were detected by ELISA,and the clinical data of PTC patients were collected. Results In 116 PCT patients,59 cases were BRAFV600Emutant and 57 cases were BRAFV600Ewild type,and 50.86%(59/116)were BRAF^V600Emutant in PTC patients. Immunohistochemical analysis showed that the HMGB1 and MMP-9 positive expression rate of BRAFV600Emutant were significantly higher than BRAF^V600Ewild type,the difference was statistically significant(P<0.05). Western blot results showed that the expression level of HMGB1 and MMP-9 of BRAF^V600Emutant was significantly higher than that of the BRAF^V600Ewild type,the difference was statistically significant(P<0.05). The serum HMGB1 and mmp-9 levels of BRAF^V600Emutant and BRAF^V600Ewild type in the PTC group were significantly higher than those in the control group,the difference was statistically significant(P<0.05),but there were no statistically significant differences in serum HMGB1 and MMP-9 levels between the BRAF^V600Emutant and the BRAF^V600Ewild type in the PTC patients(P>0.05). The proportion of BRAF^V600Emutation TNM stage Ⅲ~Ⅳ,capsular invasion,multiple lesions,and lymph node metastasis of was significantly higher than that of BRAF^V600Ewild type,the difference was statistically significant(P<0.05). Binary Logistic results showed that combined envelop infiltration,multiple lesions,positive HMGB1 and MMP-9 in tissues were all risk factors of BRAF^V600Emutation(P<0.05). Conclusion The positive expression rate of HMGB1 and MMP-9 in BRAFV600Emutant tissues of PTC patients was significantly higher than that of BRAF^V600Emutant wild type,and HMGB1 and MMP-9 positive tissues were the influencing factors of BRAF^V600Emutant.