Aurora-B激酶的表达与非小细胞肺癌患者预后及耐药的相关性分析

Study on the Relationship between High Expression of Aurora-B Kinase and Drug Resistance and Prognosis in Patients with Non-Small Cell Lung Cancer

目的检测非小细胞肺癌(NSCLC)患者病理组织中Aurora-B激酶的表达情况,并探讨其对患者预后的影响及与肿瘤耐药的相关性。方法收集194例非小细胞肺癌患者肿瘤组织标本,应用免疫组织化学方法检测Aurora-B激酶的表达情况。以Log-Rank检验比较Aurora-B激酶表达阳性患者与阴性患者总生存时间的差异,采用COX模型探索非小细胞肺癌患者预后的影响因素;分离患者肿瘤细胞进行耐药性诱导实验,并通过测量IC50的变化初步评价细胞耐药情况。结果非小细胞肺癌组织中Aurora-B激酶表达阳性率为63.92%(124/194)。Aurora-B激酶阳性患者的总生存时间低于Aurora-B激酶阴性患者(P<0.0001);COX模型显示Aurora-B激酶表达(HR=4.03,95%CI:1.80~9.01,P=0.0007)、肿瘤病理类型(HR=2.11,95%CI:1.17~3.79,P=0.0357)及临床分期(HR=0.42,95%CI:0.24~0.74,P=0.0027)是影响患者总生存时间的因素;经过耐药性诱导,Aurora-B激酶阳性肿瘤细胞IC50显著增加,且增幅高于Aurora-B激酶阴性肿瘤细胞,其差异有统计学意义(P<0.0001)。结论Aurora-B激酶在非小细胞肺癌中表达异常增高,与患者预后呈负相关,并与非小细胞肺癌耐药性相关,提示Aurora-B激酶可能成为非小细胞肺癌预后的标志物及潜在治疗靶点。

Objective To investigate the expression of Aurora-B kinase in pathological tissues from patients with non-small cell lung cancer(NSCLC),reveal its influence on prognosis of NSCLC patients and the relationship between Aurora-B kinase expression and drug resistance of NSCLC.Methods Tumor specimens of 194 patients with NSCLC were collected.The expression of Aurora-B kinase was evaluated by immunohistochemistry.Log-Rank test was used to compare the overall survival of Aurora-B kinase positive and negative patients,and COX model was applied to assess the prognostic factors for NSCLC patients.Cellular drug resistance was simply evaluated by measuring the changes of IC50 post drug resistance induction assay.Results The positive rate of Aurora-B expression in NSCLC was 63.92%(124/194).The overall survival of patients with positive Aurora-B kinase expression was lower than that of patients with negative Aurora-B kinase(P<0.0001).COX model showed that expression of Aurora-B(HR=4.02,95%CI:1.80~9.01,P=0.0007),tumor pathological type(HR=2.11,95%CI:1.17~3.79,P=0.0357)and clinical stage(HR=0.42,95%CI:0.24~0.74,P=0.0027)were the influencing factors of overall survival.After drug resistance induction,the increase of IC50 in Aurora-B positive tumor cells was significantly higher than that in Aurora-B negative tumors cells(P<0.0001).Conclusion Aurora-B was upregulated in NSCLC and negatively correlated to the prognosis of patients,and overexpression of Aurora-B was related to the drug resistance of NSCLC,suggesting that Aurora-B kinase may become a prognostic biomarker as well as a therapeutic target for NSCLC.