TGF-β1、Smad2和Smad4蛋白表达在可手术切除非小细胞肺癌中的表达

Relationship between Expression of TGF-β1, Smad2, Smad4 and Prognosis of Patients with Resected Non-small Cell Lung Cancer

背景与目的转化生长因子β(transforming growth factorβ,TGF-β)-Smad信号转导通路中任何一个环节的变化,都会导致信号传递的异常,使细胞生长分化失去控制,从而导致肿瘤发生。本研究旨在探讨可手术切除非小细胞肺癌(non-small cell lung cancer,NSCLC)TGF-β1、Smad2和Smad4的表达与预后的关系。方法应用免疫组化方法观察85例NSCLC中TGF-β1、Smad2和Smad4的表达,并分析三种蛋白的表达与临床病理因素和预后的关系。结果 TGF-β1阳性表达与肺癌分期较晚和淋巴结转移有关。Smad2的表达与各临床病理因素无关。Smad4表达阴性者较Smad4表达阳性者分期晚(P=0.014)。多因素分析显示淋巴结转移(P=0.001)是85例NSCLC的独立预后因素。47例肺腺癌多因素分析显示TGF-β1(P=0.032)和N分期(P=0.028)与预后有关。肺腺癌中TGF-β1表达阳性与生存期不良预后有关(P=0.0376)。结论 TGF-β1可能与手术切除后肺腺癌预后有关。

Background and objective It has been proven that any changes of transforming growth factor β （TGF- β）-Smad signal transduction pathway wiU lead to abnormalities of signal transmission and the out of control during cell growth and differentiation, resulting in cancer development. The aim of this study is to investigate the prognostic values of TGF-~I, Smad2 and Smad4 in resected non-small cell lung cancer （NSCLC）. Methods The expression of TGF-β1, Smad2, and Smad4 was evaluated by immunohistochemistry in 85 patients with NSCLC. The relationships among the expression of these proteins, clinicopathological factors, and prognosis were also analyzed. Results TGF-β1 positive expression was signifi- cantly correlated with the late stage and lymph node involvement. No significant association existed between the expression of Smad2 and the clinicopathological characteristics. The lack of Smad4 expression was associated with the advanced tumor stage （P=0.014）. Multivariate analysis indicated that lymph node involvement （P=0.001） was an independent prognostic factor in the 85 NSCLC patients. The positive expression levels of TGF-β1 （P=0.032） and N stage （P=0.028） were demonstrated to be independent risk factors for survival among 47 lung adenocarcinoma patients. Adenocarcinoma patients with TGF-β1 positive expression demonstrated an unfavorable survival outcome （P=0.0376）. Conclusion TGF-β1 maybe an independent predictor of survival in resected lung adenocarcinoma patients.