鞘氨醇激酶1和核因子-κBp65在非小细胞肺癌组织中的表达及与预后的关系

Expression Level of Sphingosine Kinase 1 and Nuclear Factor-κB p65 in Non-Small Cell Lung Cancer and Their Relationship with Tumor Prognosis

目的探讨鞘氨醇激酶1(SPHK1)和核因子(NF)-κB在非小细胞肺癌(NSCLC)组织中的表达及其与NSCLC浸润、转移和预后的关系。方法选取93例外科手术切除并经常规组织学检查确诊为NSCLC的标本和癌旁正常的余肺组织,应用免疫组化SP法,一抗分别为兔抗人SPHK1,NF-κB p65抗体,二抗为快捷型酶标羊抗鼠/兔IgG聚合物,检测石蜡切片的NSCLC组织SPHK1和NF-κB的表达情况。结果 SPHK1和NF-κB在NSCLC组织中的阳性率分别为96.8%(90/93)和89.2%(83/93),均高于其在正常肺组织中的阳性率18.3%(17/93),12.9%(12/93)。SPHK1和NF-κB在NSCLC组织中的表达呈正相关(r=0.464,P<0.01)。TNM分期越高,SPHK1和NF-κB p65高表达比例就越高;有淋巴结转移者的SPHK1和NF-κB p65高表达率高于无淋巴结转移组;死亡者的SPHK1和NF-κB p65高表达率高于存活者,生存分析显示SPHK1高表达组患者的生存时间短于SPHK1低表达组的生存时间(χ2=14.025,P<0.01)。结论 SPHK1可能通过NF-κB在NSCLC侵袭、转移的过程中发挥重要作用,并可能成为提示NSCLC患者预后并进行靶向治疗的指标。

Objective To investigate expression level of sphingosine kinase 1 （SPHK1） and nuclear factor-κB （NF-κB） in non-small cell lung cancer （NSCLC） and their relationships with invasion, metastasis and prognosis of NSCLC. Meth-ods Ninety-three NSCLC specimens and paraneoplastic normal lung tissue from conventional surgery were confirmed by histology. Expression of SPHK1 and NF-κB were detected by Immunohistochemistry on paraffin sections. Primary antibody were Rabbit Anti-Human SPHK1 and Rabbit Anti-Human NF-κB p65, which were incubated 1 hour in water bath. The secondary antibody was HRP-Polymer anti Mouse IgG, which was incubated 20 minutes in water bath. Results SPHK1 ex-pression was positive in 96.8% （90/93） of NSCLC specimen which is higher than in paraneoplastic normal lung tissue in which the positive rate is 18.3%（17/93）;NF-κB expression was positive in 89.2%（83/93） NSCLC which is higher than the in paraneoplastic normal lung tissue in which the positive rate is 12.9%（12/93）. The expression of SPHK1 and NF-κB in NSCLC was positively correlated （r=0.464, P＆lt;0.01）. TThe expression levels of SPHK1 and NF-κB p65 in NSCLC patients with were positively related to TNM staging and lymph node metastasis. SPHK1 expression and NF-κB p65 expression lev-el were higher in the deads than in survivals. There was no statistical significance in different expression intensity of SPHK 1 and NF-κB p65 in patients with NSCLC who had differences in gender, age, tumor size, tumor location, histological type. Survival analysis showed that survival time of patients of NSCLC with high expression of SPHK1 was shorter than those in the group with low SPHK1 expression, and the difference was statistically significant （χ2=14.025, P ＆lt; 0.01）. Conclusion In the process of NSCLC invasion and metastasis,SPHK1 may play an important role through NF-κB, and it can predict prognosis of NSCLC patient. Moreover, it will become a potential target for NSCLC target.