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目的探讨Smad4在非小细胞肺癌(NSCLC)中的表达,研究其与有丝分裂激活的蛋白激酶(MAPK)各亚族的关系和临床意义。方法应用Western印迹分析和RT-PCR方法,检测42例手术切除的肺癌标本和正常肺组织中Smad4的表达;应用免疫组化法,检测71例肺癌蜡块标本中Smad4和MAPK的亚族p38、ERK1、JNK1的表达。对各因子进行生存分析,判断对NSCLC预后的影响。结果在肺癌组织中,Smad4蛋白和mRNA的表达均低于正常组织(P<0．05);p38、ERK1和Smad4的表达与病理分期有关(P=0．000;P=0．000;P=0．005);JNK1的表达与肿瘤位置(P= 0．028)和病理分期(P=0．000)有关;Smad4和p38(P=0．000)明显相关。单因素分析显示,Smad4 (P=0．0001)、p38(P=0．0000)、JNK1(P=0．0208)、肿瘤分化(P=0．0059)和病理分期(P=0．0000)与预后相关。多因素分析显示,Smad4(P=0．019)、p38(P=0．044)、肿瘤分化(P=0．003)和病理分期(P=0．020)与预后明显相关。p38阴性而Smad4阳性的肺癌患者预后较好(P=0．000)。结论Smad4的表达在NSCLC的发生发展中可能起重要意义。在NSCLC中,ras-MAPK信号通路、转换生长因子β(TGF-β)／Smad4信号通路的主要蛋白密切相关,p38和ERK1抑制Smad4的表达。Smad4和p38可用于判断NSCLC的预后。
Objective To investigate the expression of Smad4 in non-small cell lung cancer (NSCLC) and its relationship with the subfamilies of mitogen-activated protein kinase (MAPK) and its clinical significance. Methods Western blotting and RT-PCR were used to detect the expression of Smad4 in 42 cases of lung cancer specimens and normal lung tissues. Immunohistochemistry was used to detect the expression of Smad4 and MAPK subtypes p38, ERK1, JNK1 expression. The survival of each factor analysis to determine the prognosis of NSCLC. Results The expressions of Smad4 protein and mRNA in lung cancer tissues were lower than those in normal tissues (P <0.05). The expressions of p38, ERK1 and Smad4 were correlated with pathological stage (P = 0.000; P = 0.000; P = 0.005). The expression of JNK1 was correlated with tumor location (P = 0.028) and pathological stage (P = 0.000). Smad4 and p38 (P = 0.000) were significantly correlated. Univariate analysis showed that there was no significant difference in the expression of Smad4 (P = 0.0001), p38 (P = 0.0000), JNK1 (P = 0.0208), tumor differentiation ) Is related to the prognosis. Multivariate analysis showed that Smad4 (P = 0.019), p38 (P = 0.044), tumor differentiation (P = 0.003) and pathological stage (P = 0.020) were significantly associated with prognosis. Patients with p38 negative and Smad4 positive lung cancer have a better prognosis (p = 0.000). Conclusion The expression of Smad4 may play an important role in the development of NSCLC. In NSCLC, the major proteins of the ras-MAPK signaling pathway and the transforming growth factor β (TGF-β) / Smad4 signaling pathway are closely related, and p38 and ERK1 inhibit Smad4 expression. Smad4 and p38 can be used to determine the prognosis of NSCLC.