甲状腺乳头状癌组织中Smad4基因表达水平及其意义研究

Expression and Significance of Smad4 Gene in Papillary Thyroid Cancer

目的探讨Smad4基因在甲状腺乳头状癌组织中的表达水平及其意义。方法选取2013年1—8月台州学院附属医院肿瘤外科收治的甲状腺乳头状癌患者20例作为甲状腺乳头状癌组,另选取同期本院收治的行结节性甲状腺肿手术患者20例作为对照组。收集甲状腺乳头状癌组甲状腺乳头状癌手术切除组织,对照组结节性甲状腺肿手术中腺肿旁正常组织。采用免疫组织化学检测两组Smad4阳性表达率;Western blotting法检测两组Smad4表达水平;实时荧光定量PCR法检测两组Smad4 mRNA表达水平。结果甲状腺乳头状癌组Smad4阳性表达率为35.0%（7/20）,低于对照组的90.0%（18/20）（χ^2=10.667,P=0.001）。不同性别、年龄、肿瘤直径、淋巴结转移、临床分期的甲状腺乳头状癌患者Smad4阳性表达率比较,差异均无统计学意义（P〉0.05）。甲状腺乳头状癌组Smad4表达水平为（0.352±0.012）,低于对照组的（0.722±0.007）（t=46.130,P〈0.001）。Smad4在甲状腺乳头状癌组和对照组中均有表达,甲状腺乳头状癌组Smad4 mRNA表达水平为对照组的（0.348±0.006）倍。结论 Smad4基因在甲状腺乳头状癌组织中表达下调,Smad4基因的表达缺失和下调导致转化生长因子β（TGF-β）/Smads信号通路受抑制是甲状腺乳头状癌发生、发展的可能机制之一。

Objective To explore the expression and significance of Smad4 gene in papillary thyroid cancer（ PTC）.Methods From January to August in 2013,20 cases of PTC admitted to Department of Tumor Surgery of Affiliated Hospital of Taizhou University were enrolled as the PTC group,and 20 patients with nodular goiter accepted surgery in the same period were enrolled as the control group. Surgically resected tissue of PTC in the PTC group and normal thyroid tissue adjacent to nodular goiter in the control group were collected. The positive expression of Smad4 protein in two groups was observed using immunohistochemistry,the expression level of Smad4 protein in two groups was detected using Western blotting and the expression level of Smad4 mRNA using real time-PCR. Results The positive expression rate of Smad4 protein in PTC group was 35. 0%（ 7 /20）,which was lower than 90. 0%（ 18 /20） in the control group（ χ^2= 10. 667,P = 0. 001）. There was no statistically significant difference in the positive expression rate of Smad4 protein in the PTC patients among gender,age,tumor diameter,lymph node metastases and clinical stage of PTC（ P〉0. 05）. The expression of Smad4 protein in PTC group was（ 0. 352± 0. 012）,which was lower than that in control group（ 0. 722 ± 0. 007）（ t = 46. 130,P〈0. 001）. Smad4 gene expressed in both PTC and control group,the expression level of Smad4 mRNA in PTC tissue was（ 0. 348 ± 0. 006） time as much as control group. Conclusion The expression of Smad4 gene was down-regulated in PTC. The inhibition of TGF-β / Smads signal pathway caused by the loss and down-regulation of Smad4 gene expression might be the possible mechanisms of the occurrence and development of PTC.