肺腺癌中AK2表达与EGFR突变及预后的相关性分析

Correlation analysis of AK2 expression,EGFR mutation and prognosis in lung adenocarcinoma

目的探讨腺苷酸激酶2(adenylate kinase2,AK2)在肺腺癌中的表达情况及其与表皮生长因子受体(epidermal growth factor receptor,EGFR)基因突变的相关性并分析其预后预测价值。方法选取2013年2月至2016年9月经病理学确诊的肺腺癌患者145例,利用免疫组织化学法检测AK2在肺腺癌组织中的表达,分析其与EGFR突变及临床病理特征之间的相关性;采用Kaplan-Meier法进行生存分析;以Cox比例风险回归模型进一步分析患者无疾病生存期(diseasefree survival,DFS)的影响因素。结果AK2在肺腺癌组织中的表达水平高于对应癌旁组织(P<0.001)。AK2高表达组(强染色)和弱表达组(中等、弱染色及阴性)的EGFR突变率分别为70.0%和49.4%,差异具有统计学意义(χ^2=6.117,P=0.013)。伴有EGFR突变的患者中,AK2表达与肿瘤最大径、TNM分期、淋巴结转移、胸膜侵犯、突变类型显著相关(P<0.05),而与其他临床特征无相关性。生存分析表明,在EGFR突变患者中,AK2高表达组和弱表达组的中位DFS分别为15.0和21.0个月,差异有统计学意义(χ^2=5.126,P=0.024);而EGFR未突变患者AK2高表达与弱表达患者的中位DFS差异无统计学意义(χ^2=2.467,P=0.117)。单因素分析显示,AK2水平、EGFR突变、肿瘤最大径、TNM分期、淋巴结转移和胸膜侵犯均为影响肺腺癌患者DFS的因素;进一步进行多因素Cox比例风险回归模型分析表明,AK2高表达(HR=1.555,95%CI:1.021~2.369,P=0.040)和淋巴结转移(HR=1.953,95%CI:1.181~3.230,P=0.009)为肺腺癌患者DFS的独立影响因素。结论肺腺癌组织AK2表达水平与EGFR突变率呈正向关联,癌组织高表达AK2预示较差的预后。

Objective To understand the relationship between the expression of adenylate kinase 2 (AK2),epidermal growth factor receptor (EGFR) mutation and clinicopathological features,prognosis in patients with lung adenocarcinoma (LAD).Methods The expression of AK2 was detected by immunohistochemistry in 145 cases with LAD from Affiliated Tumor Hospital of Xinjiang Medical University during February 2013 to September 2016.The relationship between AK2 expression,EGFR mutation status and clinical characteristics,disease-free survival (DFS) was analyzed by Chi-square test,Kaplan-Meier method and Cox proportional hazards regression model.Results Higher AK2 level was observed in lung adenocarcinoma tissue compared with adjacent peritumoral tissues.The EGFR mutation rates were70.0% and 49.4% in patients with higher(strongly positive) and weak (low,moderately or mildly positive,negative) expression of AK2 respectively,the difference was significant (χ^2=6.117,P=0.013).The expression of AK2 in LAD patients with EGFR mutation was related with tumor size,clinical stage, lymph node metastasis,pleural invasion and EGFR mutation type (P<0.05).The median DFS in LAD patients with EGFR mutation presented significant difference in AK2 high-expression (15.0 months) group and AK2 weak-expression (21.0 months) group (χ^2=5.126,P=0.024),while there was no significant difference in LAD patients without EGFR mutation (χ^2=2.467,P=0.117) between the two groups.Univariate survival analysis indicated that level of AK2,EGFR mutation status,tumor size,TNM stage, lymph node metastasis and pleural invasion could act as significant prognostic factors for DFS,while multivariate survival analysis showed that AK2 expression (HR=1.555,95%CI:1.021-2.369,P=0.040) and lymph node metastasis (HR=1.953,95%CI: 1.181-3.230,P=0.009) could predict prognosis independently for DFS.Conclusion The expression level of AK2 is greatly related with the mutation rate of EGFR in LAD patients,higher AK2 level will indicate poor prognosis.