非小细胞肺癌中STAT3与MAPK的表达及临床意义

Expression of STAT3 and MAPK in Non-small Cell Lung Cancer and Their Clinical Significance

目的:探讨STAT3和MAPK的几个主要亚族p38、ERK1和JNK1在非小细胞肺癌中的表达,判断这几种信号蛋白的相互关系及对非小细胞肺癌预后的影响。方法:应用免疫组化的方法对71例手术标本的石蜡切片进行染色,判断STAT3和MAPK几个主要亚族在肺癌组织中的表达。结果:p38、ERK1和STAT3的表达与临床分期有关(P<0.01)。JNK1的表达与肿瘤位置(P=0.028)和临床分期(P=0.000)有关。STAT3和p38明显相关(P=0.000)。单因素分析显示STAT3(P=0.0006)、p38(P=0.0000)、JNK1(P=0.0208)、肿瘤分化(P=0.0059)和临床分期(P=0.0000)与预后相关。多因素分析显示STAT3(P=0.025)、p38(P=0.026)、肿瘤分化(P=0.003)和临床分期(P=0.019)与预后明显相关。结合STAT3和p38两个因子进行预后分析,发现两个指标均阴性表达时,非小细胞肺癌患者预后较好(P<0.05)。结论:JAK-STAT和ras-MAPK两大信号传导通路的几个主要蛋白的表达对于非小细胞肺癌的诊治有一定的临床意义;STAT3的表达能促进p38的表达;二者的表达可辅助用于对非小细胞肺癌预后的评估。

Objective: To explore the expression of STAT3 and several main subtribes of MAPK in non-small cell lung cancer(NSCLC), the relationship among these signal transduction proteins, and their influence on prognosis of non-small cell lung cancer. Methods: Seventy-one paraffin sections of patients between 1996 and 1997 were studied using immunohistochemistry to clarified the expression of these several proteins. Results: The expression of p38, ERK1 and STAT3 was associated with clinical staging (P<0.01); and JNK1 with tumor location (P=0.028) and clinical staging (P=0.000). There was a correlation between p38 and STAT3 (P=0.000). The expression of STAT3 (P=0.000 6), p38 (P=0.000 0) and JNK1 (P=0.020 8), tumor differentiation (P=0.005 9) and clinical staging (P=0.000 0) were significantly correlated with prognosis of non-small cell lung cancer by univariate analysis, and STAT3 (P=0.025), p38 (P=0.026), tumor differentiation (P=0.003), and clinical staging (P=0.019) were correlated with prognosis by multivariable analysis. Using p38 and STAT3 together, we found that the negative expression of both p38 and STAT3 linked with better prognosis of NSCLC (P<0.05). Conclusion: Of several proteins in the two signal transduction pathways, the expression of STAT3 can motivate that of p38, and the expression of these two proteins can help to predict the prognosis of NSCLC.