分化型甲状腺癌中TGF-β_1和BMP-7的表达及与临床病理和预后的关系
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摘要
目的研究转化生长因子-β_1(TGF-β_1)和骨形态发生蛋白-7(BMP-7)在分化型甲状腺癌(DTC)组织中的表达及其与临床病理及预后的关系。方法收集DTC存档蜡块78例,对照组存档蜡块22例(正常甲状腺组织标本12例,结节性甲状腺肿组织标本10例)。应用免疫组织化学法(SP法),检测TGF-β_1和BMP-7在DTC中的表达。结果 TGF-β_1在DTC细胞浆中呈黄色或棕褐色强阳性表达,78例DTC TGF-β_1阳性表达50例,阳性表达率为64.10%,与正常甲状腺(2/12)和结节性甲状腺肿(2/10)比较,差异有统计学意义(P<0.05)。结节性甲状腺肿和正常甲状腺组织中TGF-β_1表达差异无统计学意义(P>0.05)。BMP-7在DTC中细胞浆内呈弱表达或不表达,与正常甲状腺和结节性甲状腺肿比较,差异有统计学意义(P<0.05)。DTC的TGF-β_1和BMP-7的阳性表达在性别、年龄、肿瘤大小和病理类型之间的表达差异无统计学意义(P>0.05),在淋巴结转移及病理分期间差异有统计学意义(P<0.05)。TGF-β_1和BMP-7在DTC中表达呈负相关(r=-0.315,P<0.05)。结论 TGF-β_1和BMP-7介导的Smad信号通路参与了DTC的发生发展过程。
Objective To investigate the expressions of TGF-β_1 and BMP-7 in differentiated thyroid carcinoma( DIC) and their correlation with clinicopathological characteristics and prognosis of patients. Methods A total of 78 patients with DIC who were treated in our hospital from March 2010 to August 2016 were enrolled in the study. The tissues specimens of patients were collected as TIC group,at the same time,the other 22 tissues specimen were collected as control group,including 12 cases of normal thyroid tissues and 10 cases of nodular goiter tissues. The expression levels of TGF-β_1 and BMP-7 were detected by immunohistochemistry( SP). Results The expression of TGF-β_1 was positive in cytoplasm of DTC in yellow or tan-positive expression. Among 78 cases of DIC tissues,the positive expression rate of TGF-β_1 was 64. 10%( 50/78),which was significantly higher than that in normal thyroid tissues( 2/12) and that in nodular goiter tissues( 2/10)( P <0. 05). However there were no significant differences in the expression levels of TGF-β_1 between nodular goiter tissues and normal thyroid tissues( P > 0. 05). Moreover BMP-7 was weakly expressed or not expressed in cytoplasm of DTC,there were5 cases( 6. 41%) of positive expression in DIC group,and which was significantly different from that in normal thyroid tissues( 10/12,83. 33%) and nodular goiter tissues( 8/10,80. 00%)( P < 0. 05). In addition there were no significant differences in the expression levels of TGF-β_1 and BMP-7 in DTC group among patient's gender,age,tumor size and pathological type( P > 0. 05),however,there were significant differences in lymph node metastasis and pathological stage( P < 0. 05). Besides the expression levels of TGF-β_1 were negatively correlated with those of BMP-7 in DTC group( r =-0. 315,P < 0. 05).Conclusion TGF-β_1 and BMP-7-mediated Smad signaling pathway is involved in the pathogenesis and developement of DTC.
Objective To investigate the expressions of TGF-β_1 and BMP-7 in differentiated thyroid carcinoma( DIC) and their correlation with clinicopathological characteristics and prognosis of patients. Methods A total of 78 patients with DIC who were treated in our hospital from March 2010 to August 2016 were enrolled in the study. The tissues specimens of patients were collected as TIC group,at the same time,the other 22 tissues specimen were collected as control group,including 12 cases of normal thyroid tissues and 10 cases of nodular goiter tissues. The expression levels of TGF-β_1 and BMP-7 were detected by immunohistochemistry( SP). Results The expression of TGF-β_1 was positive in cytoplasm of DTC in yellow or tan-positive expression. Among 78 cases of DIC tissues,the positive expression rate of TGF-β_1 was 64. 10%( 50/78),which was significantly higher than that in normal thyroid tissues( 2/12) and that in nodular goiter tissues( 2/10)( P <0. 05). However there were no significant differences in the expression levels of TGF-β_1 between nodular goiter tissues and normal thyroid tissues( P > 0. 05). Moreover BMP-7 was weakly expressed or not expressed in cytoplasm of DTC,there were5 cases( 6. 41%) of positive expression in DIC group,and which was significantly different from that in normal thyroid tissues( 10/12,83. 33%) and nodular goiter tissues( 8/10,80. 00%)( P < 0. 05). In addition there were no significant differences in the expression levels of TGF-β_1 and BMP-7 in DTC group among patient's gender,age,tumor size and pathological type( P > 0. 05),however,there were significant differences in lymph node metastasis and pathological stage( P < 0. 05). Besides the expression levels of TGF-β_1 were negatively correlated with those of BMP-7 in DTC group( r =-0. 315,P < 0. 05).Conclusion TGF-β_1 and BMP-7-mediated Smad signaling pathway is involved in the pathogenesis and developement of DTC.
引文
1刘春梅,孙小霞,杨亚峰.mi R-142影响甲状腺癌细胞增殖分化的机制研究.肿瘤药学,2017,1:17-22.
2 郑齐锶,严留佳,王庆飞.骨形态发生蛋白-7在胃癌组织中的表达及意义.现代检验医学杂志,2015,6:18-24.
3 Pilotti S,Collini P,Del Bo R,et al.A novel panel of antibodies that segregrates immunocytochemically poorly differentiated carcinoma from undifferentiated carcinma of the thyroid gland.Am J Surg Pathol,1994,18:1054-1064.
4 陈蕾,柳玉红,邹桂华.FAK和Src在甲状腺乳头状癌中的表达及其在肿瘤侵袭转移中的临床意义及机制研究.现代肿瘤医学,2017,6:876-880.
5 李仕亮,孙纷纷,邵国安.甲状腺癌中PTEN蛋白表达与BARFV600E突变的相关性研究.现代肿瘤医学,2017,6:871-875.
6 瑞青,吴永昌,邹海,等.不同血清肿瘤标志物对胃癌诊断价值的临床研究.现代检验医学杂志,2014,29:102-106.
7 赵亚,刘慧,高全立.转化生长因子-β1、白细胞介素-6和肿瘤坏死因子-1在乳腺肿瘤患者血清中的水平.中华实验外科杂志,2015,12:3153-3156.
8 张琳,吕志栋,刘相萍等.转化生长因子-β1通过诱导上皮间充质转化促进乳腺癌细胞侵袭转移的研究.中华实验外科杂志,2015,32:979-982.
9 Shao XC,Ju LL.Fn14,a downstream target of the TGF-βsignaling pathway,regulates fibroblast activation.Plo S one,2015,12:802-809.
10 Jing L,Li PC,Wei W,et al.The role,mechanism and potentially novel biomarker of micro RNA-17-92 cluster in macrosomia.Scientific reports,2015,10:212-219.
11 刘楠楠,于春艳,王丹.Smad4蛋白在良恶性甲状腺病变组织中的表达及意义.中国老年学杂志,2017,3:1077-1078.
12 Alarmo EI,Parssinen J,Ketolainen JM,et al.BMP7 in uences proliferation,migration,and invasion of breast cancer cells.Cancer Lett,2009,275:35-43.
13 Sakai H,Furihata M,Matsuda C,et al.Augmented autocrine bone morphogenic protein(BMP)7 signa—ling increases the metastatic potential of mouse breastcancer cells.Clin Exp Metastasis,2012,29:327-338.
14 丁咪,李全民.骨形态发生蛋白7在糖尿病肾病中的作用及治疗进展.医学综述,2017,4:738-741.
15 刘飞.骨形态发生蛋白与肿瘤关系的研究新进展.实用骨肿瘤学杂志,2007,21:188-190.
16 Sakai H,Furihata M,Matsuda C,et al.Augmented autocrine bone morphogenic protein(BMP)7 signa—ling increases the metastatic potential of mouse breast cancer cells.Clin Exp Metastasis,2012,29:327-338.
2 郑齐锶,严留佳,王庆飞.骨形态发生蛋白-7在胃癌组织中的表达及意义.现代检验医学杂志,2015,6:18-24.
3 Pilotti S,Collini P,Del Bo R,et al.A novel panel of antibodies that segregrates immunocytochemically poorly differentiated carcinoma from undifferentiated carcinma of the thyroid gland.Am J Surg Pathol,1994,18:1054-1064.
4 陈蕾,柳玉红,邹桂华.FAK和Src在甲状腺乳头状癌中的表达及其在肿瘤侵袭转移中的临床意义及机制研究.现代肿瘤医学,2017,6:876-880.
5 李仕亮,孙纷纷,邵国安.甲状腺癌中PTEN蛋白表达与BARFV600E突变的相关性研究.现代肿瘤医学,2017,6:871-875.
6 瑞青,吴永昌,邹海,等.不同血清肿瘤标志物对胃癌诊断价值的临床研究.现代检验医学杂志,2014,29:102-106.
7 赵亚,刘慧,高全立.转化生长因子-β1、白细胞介素-6和肿瘤坏死因子-1在乳腺肿瘤患者血清中的水平.中华实验外科杂志,2015,12:3153-3156.
8 张琳,吕志栋,刘相萍等.转化生长因子-β1通过诱导上皮间充质转化促进乳腺癌细胞侵袭转移的研究.中华实验外科杂志,2015,32:979-982.
9 Shao XC,Ju LL.Fn14,a downstream target of the TGF-βsignaling pathway,regulates fibroblast activation.Plo S one,2015,12:802-809.
10 Jing L,Li PC,Wei W,et al.The role,mechanism and potentially novel biomarker of micro RNA-17-92 cluster in macrosomia.Scientific reports,2015,10:212-219.
11 刘楠楠,于春艳,王丹.Smad4蛋白在良恶性甲状腺病变组织中的表达及意义.中国老年学杂志,2017,3:1077-1078.
12 Alarmo EI,Parssinen J,Ketolainen JM,et al.BMP7 in uences proliferation,migration,and invasion of breast cancer cells.Cancer Lett,2009,275:35-43.
13 Sakai H,Furihata M,Matsuda C,et al.Augmented autocrine bone morphogenic protein(BMP)7 signa—ling increases the metastatic potential of mouse breastcancer cells.Clin Exp Metastasis,2012,29:327-338.
14 丁咪,李全民.骨形态发生蛋白7在糖尿病肾病中的作用及治疗进展.医学综述,2017,4:738-741.
15 刘飞.骨形态发生蛋白与肿瘤关系的研究新进展.实用骨肿瘤学杂志,2007,21:188-190.
16 Sakai H,Furihata M,Matsuda C,et al.Augmented autocrine bone morphogenic protein(BMP)7 signa—ling increases the metastatic potential of mouse breast cancer cells.Clin Exp Metastasis,2012,29:327-338.