PI3K/Akt信号传导通路蛋白在晚期非小细胞肺癌中的表达及临床意义

目的：探讨磷脂酰肌醇3-激酶（phosphatidyl inositol 3-kinase，PI3K），磷酸化蛋白激酶B（phosphorylated Akt B，p-AKT）在晚期非小细胞肺癌（non-small-cell lung carcinoma，NSCLC）组织中的表达及其与预后的关系。方法：回顾性分析87例晚期NSCLC患者的临床资料，其中鳞癌组37例，腺癌组50例，并收集16例肺癌癌旁正常肺组织标本作为对照组。应用免疫组织化学方法检测PI3K和p-AKT蛋白在癌组织和正常组织中的表达，分析其与患者临床资料变量的关系及其对预后的影响。结果：PI3K和p-AKT在晚期NSCLC中的表达明显高于正常肺组织（P=0.001，0.005）。p-AKT表达与肿瘤的TNM分期呈正相关（P=0.016），而与肿瘤的性别、年龄、病理类型、分化程度、体力状态（PS）评分无关。PI3K表达与上述临床特征无关。PI3K阴性表达组的中位数生存时间明显优于阳性表达组17.699月（95%CI 15.114-20.283）/13.426月（95%CI 11.832-15.021），P=0.004]，p-AKT阴性表达组的中位数生存时间明显亦优于阳性表达组17.134月（95%CI 14.927-19.341）/13.067月（95%CI 11.316-14.817），P=0.007]。多变量Cox回归分析显示PI3K （HR=2.128，P=0.009），p-AKT （HR=0.501，P=0.045），TNM分期（HR=4.808，P〈0.001），PS评分（HR=3.277，P〈0.001）是晚期NSCLC的独立预后因素。结论：PI3K、p-AKT与晚期NSCLC不良预后因素密切相关，PI3K、p-AKT是晚期NSCLC预后的独立不利因素。

Expression and clinical significance of the PI3K/Akt signal transduction pathway in advanced non-small cell lung carcinoma

Objective：To investigate the expression of phosphatidylinositol 3-kinase（PI3K） and phosphorylated Akt B （p-Akt） protein and its relationship to prognosis in advanced non-small-cell lung carcinoma （NSCLC）. Methods：The clini-cal records of 87 patients with advanced NSCLC, consisting of 37 cases with squamous cell carcinoma （SCC） and 50 cases with adenocarcinoma （AdC）, together with 16 tumor-adjacent normal tissues, were retrospectively evaluated. PI3K and p-Akt expression were measured by using an immunohistochemical method and its association with clinicopathological data and prognosis were also evaluated. Results：PI3K and p-Akt expression was significantly higher in cancer tissues than that in tumor-adjacent normal tissues （P=0.001,0.005;respectively）. The overexpression of p-Akt was only related to TNM stage （P=0.016） and no correlation was observed with gender, age, histological categories, histological grade, and ECOG perfor-mance status. The overexpression of PI3K was not related to the above clinicopathological variables. The survival was sig-nificantly better in patients with PI3K and p-Akt negative expression than with positive expression 17.699 months （95%CI 15.114-20.283）/13.426 months （95%CI 11.832-15.021）,P=0.004 and 17.134 months （95%CI 14.927-19.341）/13.067 months （95%CI 11.316-14.817）,P=0.007]. Multivariate analysis showed that PI3K （HR=2.128,P=0.009）, p-Akt （HR=0.501,P=0.045）,TNM stage （HR=4.808,P〈0.001） and ECOG performance status （HR=3.277,P〈0.001） were independent predictors for survival in advanced NSCLC. Conclusion：PI3K and p-Akt overexpression are independent prognostic mark-ers and potential new therapeutic targets in advanced NSCLC.