Fn14与JAK/STAT在非小细胞肺癌EGFR外显子19缺失突变组织中的表达

Analysis on the correlation of Fn14 and JAK/STAT signal pathway in non-small cell lung cancer with EGFR exon 19 deletion

目的探讨成纤维细胞生长因子诱导14(Fn14)和Janus激酶/信号转导子和转录激活子(JAK/STAT)信号分子在非小细胞肺癌(NSCLC)EGFR外显子19缺失突变(EGFR 19-Del)组织样本中的表达情况。方法经突变扩增阻滞系统法筛选出125例EGFR 19-Del的NSCLC组织并收集30例配对癌旁组织,应用免疫组织化学法检测该组织样本中Fn14、pJAK1和p-STAT1的表达,统计分析3种蛋白表达与临床病理特征的关系及三者之间的相关性。结果 Fn14阳性表达主要定位于细胞膜和胞质,p-JAK1、p-STAT1阳性表达主要定位于细胞质和胞核。EGFR 19-Del的NSCLC组织中Fn14、p-JAK1、pSTAT1的阳性表达率分别为100.0%(125/125)、83.2%(104/125)和100.0%(125/125),均高于癌旁组织,差异有统计学意义(P<0.05)。三者在性别、年龄、吸烟史、病理类型方面的表达差异均无统计学差意义(P>0.05),在组织学分级、pT NM分期、淋巴结转移方面的表达差异均有统计学意义(P<0.05)。Fn14与p-JAK1、p-STAT1在病理类型、组织学分级及pT NM分期方面表达均有很好的相关性(P<0.05,r>0.3)。结论 Fn14、p-JAK1、p-STAT1在EGFR 19-Del的NSCLC组织中呈高表达,表明Fn14、p-JAK1、p-STAT1很可能与EGFR 19-Del的NSCLC发生、发展有关;且Fn14可能促进p-JAK1、p-STAT1的表达,为进一步研究Fn14在EGFR 19-Del的NSCLC中的作用机制提供重要依据。

Objective To explore the expression of fibroblast growth factor-inducible 14（ Fn14） and Janus kinase/signal transducerand activator of transcription（ JAK / STAT） in non-small cell lung cancer（ NSCLC） tissues with EGFR exon 19 deletion.Methods In this study,125 NSCLC cases with EGFR 19-Del were selected by amplification refractory mutation system. And the 30 cases of paired adjacent normal tissues were collected. Expressions of Fn14,p-JAK1 and p-STAT1 were detected in these samples using immunohistochemistry and the correlation of Fn14 expression with JAK / STAT expression was analyzed by statistics. Results The expression of Fn14 was mainly located on cell membrane and cytoplasm,while the expression of p-JAK1 and p-STAT1 were mainly located in cytoplasm and cell nucleus. Compared to normal lung tissues,the higher expression rates of Fn14,p-JAK1 and p-STAT1 protein were 100. 0%（ 125 /125）,83. 2%（ 104 /125） and 100. 0%（ 125 /125） in NSCLC tissues with EGFR 19-Del（ P〈 0. 05）.There were significant differences of Fn14,p-JAK1 and p-STAT1 expression in histological grades,pT NM stages and lymph node metastasis（ P〈 0. 05）,while there were no significant differences in sex,age,smoking history and pathological types（ P〉 0. 05）. The correlation of Fn14 with p-JAK1 and p-STAT1 were obvious（ P〈 0. 05,r 〉 0. 3） in pathological classification,histological grads and pT NM stage of NSCLC. Conclusion Fn14,p-JAK1 and p-STAT1 proteins are highly expressed in NSCLC with EGFR 19-Del,suggesting that the above three proteins would be likely to associate with the development of NSCLC. The good correlations between Fn14expression and p-JAK1,p-STAT1 hints that Fn14 may effect on the expression of p-JAK1,p-STAT1. All these provide important basis for the mechanism study of Fn14 affecting on the development of NSCLC with EGFR 19-Del.