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

Abstract

Background and objective: It has been proven that any changes of transforming growth factor β (TGF-β)-Smad signal transduction pathway will 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-β1, 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 significantly 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).

Conclusions: TGF-β1 may be an independent predictor of survival in resected lung adenocarcinoma patients. .

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非小细胞肺癌TGF-β1、Smad2和Smad4的表达。A：肺鳞癌表达TGF-β1，呈细胞浆阳性（SP，×200）；B：肺腺癌表达Smad2，呈细胞核阳性（SP，×200）；C：肺鳞癌表达Smad4，呈细胞浆阳性（SP，×400）；D：阴性对照（SP，×400） TGF-β1, Smad2, and Smad4 expression in non-small cell lung cancer. A: TGF-β1 expression in lung squamous carcinoma (cellular localization in cytoplasm) (×200); B: Smad2 expression in lung adenocarcinoma (cellular localization in nucleus) (×200); C: Smad4 expression in lung squamous carcinoma (cellular localization in cytoplasm) (×400); D: Negative control (×400)

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NSCLC患者TGF-β1表达阴性组和阳性组的生存曲线。A：NSCLC患者TGF-β1表达阴性组和阳性组的生存曲线；B：肺腺癌患者TGF-β1表达阴性组和阳性组的生存曲线 Influence of TGF-β1 expression on overall survival. A: Influence of TGF-β1 expression on overall survival in NSCLC patients (Kaplan-Meier multivariate analysis); B: Influence of TGF-β1 expression on overall survival in lung adenocarcinoma patients (Kaplan-Meier multivariate analysis)

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NSCLC患者Smad2和Smad4表达阴性组和阳性组的生存曲线。A：NSCLC患者Smad2表达阴性组和阳性组的生存曲线；B：NSCLC患者Smad4表达阴性组和阳性组的生存曲线 Influence of Smad2 and Smad4 expression on overall survival. A : Influence of Smad2 expression on overall survival in NSCLC patients (Kaplan-Meier multivariate analysis); B: Influence of Smad4 expression on overall survival in NSCLC patients (Kaplan-Meier multivariate analysis)