TLR信号通路关键因子在肺腺癌组织中的表达与临床意义

Expression of TLR-mediated signaling pathway in human lung adenocarcinoma and its correlation with clinicopathologic features

目的研究Toll样受体(Toll-like receptors,TLR)介导的信号通路关键因子:Toll样受体4 (TLR4)、核因子κB(NF-κB)、髓样分化因子88(MyD88)、白介素-1受体相关激酶-1(IRAK1)、IRAK4以及肿瘤坏死因子受体相关因子6(TRAF6)在肺腺癌组织中的表达与临床意义。方法分别采用免疫组化SP法和RT-PCR法检测92例肺腺癌组织和30例正常肺组织中TLR4、NF-κB、MyD88、IRAK1、IRAK4、TRAF6的表达情况并作比较分析。结果肺腺癌组织中TLR4、NF-κB、MyD88、IRAK1、IRAK4蛋白的表达水平均明显高于正常肺组织(均P<0.05)。不同性别、年龄、肿瘤大小、分化程度患者TLR4、NF-κB、MyD88、IRAK1、IRAK4蛋白比较差异均无统计学意义(均P>0.05),而不同程度淋巴结转移、临床分期、远处转移患者上述蛋白比较差异均有统计学意义(均P<0.05);不同性别、年龄、肿瘤大小、分化程度、淋巴结转移、临床分期、远处转移患者TRAF6蛋白比较差异均无统计学意义(均P>0.05)。肺腺癌组织TLR4、NF-κB、MyD88、IRAK1、IRAK4 mRNA的表达水平均明显高于正常肺组织(均P<0.05),而TRAF6 mRNA的表达水平与正常肺组织比较无统计学差异(P>0.05)。结论 TLR4、NF-κB、MyD88、IRAK1、IRAK4在肺腺癌中的高表达与肺腺癌的发生、发展及预后密切相关。

Objective To investigate the expression of TLR-mediated signaling pathway and its downstream key factors in human lung adenocarcinoma and to analyze their correlation with clinicopathologic features of lung adenocarcinoma.Methods The protein and m RNA expressions of Toll-like receptors 4(TLR4), nuclear factor kappa-B(NF-κB), myeloid differentiation factor 88(MyD88), Interleukin-1 receptor-associated kinase 1(IRAK1), Interleukin-1 receptor-associated kinase 4(IRAK4) and TNF receptor associated factor 6(TRAF6) in cancer tissue samples of 92 lung adenocarcinoma patient and30 samples of normal lung tissue were detected by immunohistochemistry and Real-time PCR, respectively. Results The immunohistochemistry demonstrated that the expression level of TLR4, NF-κB, MyD88, IRAK1 and IRAK4 in lung adenocarcinoma patient tissues were significantly higher than that in normal lung tissues(all P<0.05). The high expression of TLR4, NF-κB,MyD88, IRAK1 and IRAK4 were positively associated with tumor stage, lymph node metastasis and distant metastasis(all P<0.05). Results from Real-time PCR showed that m RNA expression of TLR4, NF-κB, MyD88, IRAK1 and RAK4 in lung adenocarcinoma patient tissues were significantly higher than that in normal lung tissues while TRAF6 m RNA expression showed no significant difference when compared with normal lung tissues(P>0.05). Conclusion The results indicate that high expression of TLR4, NF-κB, MyD88, IRAK1 and IRAK4 may be closely related to the occurrence, development and prognosis of lung adenocarcinoma.