Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis
Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis
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DOI：
10.1016/j.lungcan.2005.10.003
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发表时间：
2006-02-01
期刊：
影响因子：
5.3
通讯作者：
Chang, XJ
中科院分区：
文献类型：
--
作者：
Tang, JM;He, QY;Chang, XJ
Akt是磷脂酰肌醇3-激酶（PI3K）的下游介质，是在肿瘤发生中起中心作用的信号转导蛋白。抑癌基因PTEN负性调节PI3K/Akt信号通路。然而，At和PTEN功能在非小细胞肺癌（NSCLC）患者中的作用尚未完全确定。目的探讨磷酸化At（p-Akt）表达和PTEN表达缺失在非小细胞肺癌生物学行为及预后中的作用。采用免疫组化法检测20例正常肺组织和102例NSCLC组织中p-Akt和PTEN的表达。所有NSCLC患者随访3~60个月。NSCLC组织中p-Akt表达阳性率为41.2%（42/102），PTEN表达缺失率为46.1%（47/102），而正常肺组织中p-Akt表达阴性（0%，0/20），PTEN表达阳性（100%，20/20）。p-Akt过表达和PTEN表达缺失与肿瘤分化程度低、淋巴结转移、远处转移和临床分期晚有关。p-Akt与PTEN的表达呈显著负相关（r =-0.425，P <0.001）。p-Akt表达阳性（42/102）和PTEN表达缺失（47/102）患者的5年生存率和中位生存时间均明显低于p-Akt表达阴性者14个月组和32个月组的PTEN阳性表达率分别为14.29%和33.33%，Logrank检验χ 2 = 14.24，P <0.001（10.64%vs38.18%，15个月vs40个月，对数秩检验卡方（2）= 21.06，P <0.001）。单因素分析显示吸烟、肿瘤大小、淋巴结转移、远处转移、分期、p-Akt和PTEN表达缺失是影响预后的重要因素。多因素考克斯分析结果显示，吸烟、分期和PTEN表达缺失是独立的影响因素。p-Akt在NSCLC的临床标本中过表达并伴有PTEN的丢失。p-Akt和PTEN均与非小细胞肺癌的侵袭和转移有关。PTEN表达缺失是NSCLC患者预后不良的独立因素。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Akt, a downstream mediator of phosphatidylinositol 3-kinase (PI3K), is a signal transduction protein that plays a central role in tumorigenesis. The tumor suppressor gene PTEN negatively regulates the PI3K/Akt signaling pathway. However, the roles of At and PTEN function in patients with non-small cell lung cancer (NSCLC) is not well established. To clarify roles of expression of phosphorylated At (p-Akt) and toss of PTEN expression in biological behavior and prognosis of NSCLC. Immunohistochemical staining was used to determine the expression of p-Akt and PTEN in 20 cases of normal lung tissues and 102 cases patients with NSCLC. ALL patients with NSCLC were followed from 3 to 60 months. The positive incidence of p-Akt expression and Loss incidence of PTEN expression in NSCLC were 41.2% (42/102) and 46.1% (47/102), while negative of p-Akt expression (0%, 0/20) and positive of PTEN expression (100%, 20/20) in normal lung tissues. Overexpression of p-Akt and Loss of PTEN expression were correlated to poor differentiation, lymph node involvement, distant metastasis and late stages. A significant negative correlation was observed between expression of p-Akt and PTEN (r = -0.425, P < 0.001). Patients with p-Akt positive expression (42/102) and loss of PTEN expression (47/102) showed significantly worse 5 years survival rate and median survival time than relevant those with p-Akt negative expression (14.29% versus 33.33%, 14 months versus 32 months, Logrank test chi(2) = 14.24, P < 0.001) and PTEN positive expression (10.64% versus 38.18%, 15 months versus 40 months, Log-rank test chi(2) = 21.06, P < 0.001). A univariate analysis revealed that smoking, tumor size, lymph node involvement, distant metastasis, stage, p-Akt and loss of PTEN expression were significant correlative factors with prognosis. The result of multivariate Cox analysis showed that smoking, stage and loss of PTEN expression were independent prognosticators. p-Akt is overexpressed and accompanied by the loss of PTEN in clinical specimens of NSCLC. Both p-Akt and PTEN are concerned with invasion and metastasis of NSCLC. Loss of PTEN expression is an independent poor prognostic factor for patients with NSCLC. (c) 2005 Elsevier Ireland Ltd. All rights reserved.