转化生长因子-β1、Smad3、Smad4和Smad7在结直肠癌发生中的作用

Roles of Transforming Growth Factor-β1, Smad3, Smad4 and Smad7 in the Development of Colorectal Cancer

背景:结直肠腺瘤-腺癌序列是目前公认的结直肠癌发生学说,但关于结直肠腺瘤,特别是高危型结直肠腺瘤中转化生长因子(TGF)-β1通路蛋白表达的临床研究较少。目的:探讨TGF-β1、Smad3、Smad4和Smad7在结直肠癌发生中的作用。方法:选取2000年8月～2006年12月六安市人民医院结直肠息肉标本110例(包括腺瘤性和非腺瘤性息肉)、结直肠癌40例和正常结直肠组织20例,以免疫组化染色检测TGF-β1、Smad3、Smad4和Smad7在各组中的表达,并分析高危型腺瘤中TGF-β1、Smad3、Smad4和Smad7表达与临床病理特征的关系。结果:TGF-β1、Smad3、Smad4、Smad7在息肉组、结直肠癌组和对照组中的表达有显著差异(P<0.05),其表达与高危型腺瘤患者的临床病理特征均不相关。高危型腺瘤和Dukes A期结直肠癌中TGF-β1、Smad3、Smad7的表达有显著差异(P<0.05),而Smad4表达无显著差异。结论:TGF-β1通路可能参与了结直肠癌的发生过程,TGF-β1、Smad3和Smad7可能在结直肠腺瘤的癌变早期起作用。

Background： Colorectal adenoma-adenocarcinoma sequence is the accepted hypothesis of tumorigenesis of colorectal cancer. However, clinical studies about the expression of transforming growth factor （TGF）-β1 pathway protein in colorectal adenoma, especially in high risk colorectal adenoma are rare. Aims： To explore the roles of TGF-β1, Smad3, Smad4 and Smad7 in the development of colorectal cancer. Methods： One hundred and ten cases of colorectal polyps （including adenomatous polyp and non-adenomatous polyp）, 40 colorectal cancer and 20 normal colorectal tissues in Liu＇an People＇s Hospital from Aug. 2000 to Dec. 2006 were enrolled. Expression of TGF-β1, Smad3, Smad4 and Smad7 were detected by immunohistochemistry. The relationship between expression of TGF-IM, Smad3, Smad4 and Smad7 and clinicopathologic features in high risk adenoma was analyzed. Results： Statistical differences in expression of TGF-IM, Smad3, Smad4 and Smad7 were found in polyps group, colorectal cancer group and control group （P〈0.05）. No significant relationship was found between clinicopathologic features in high risk adenoma and expression of TGF-β1, Smad3, Smad4 and Smad7. Expression of TGF-IM, Smad3 and Smad7 in high risk adenoma was significantly higher than those in colorectal cancer of Dukes A stage （P〈0.05）, but not Smad4. Conclusions： TGF-IM pathway may be involved in the tumorigenesis of colorectal cancer, and expression of TGF-β1, Smad3 and Smad7 may play some roles in the early stage of carcinogenesis of colorectal adenoma.