摘要
目的探讨磷脂酰肌醇3激酶（P13K）p110α蛋白在非小细胞肺癌组织中的表达及其作用机制。方法采用免疫组化法检测非小细胞肺癌组织中P13Kpll0α和P13K通路其他蛋白的表达，以及Pik3ca启动子调节因子p53的突变状态。分析P13Kp110α的表达与患者临床病理特征、P13K通路其他蛋白表达以及p53突变状态的关系。结果170例非小细胞肺癌患者中，P13Kpll0α低表达72例（42．4％），高表达98例（57．6％）。患者的性别、年龄、T分期和病理学分级与P13Kp110α的高表达均无关（均P〉0．05）；患者的吸烟情况、病理学分型、N分期、TNM分期和Ki．67计数与P13Kplloa高表达均有关（均P〈0．05）。P13KpllOa的表达与MET和突变型表皮生长因子受体（EGFR）的表达均有关（均P〈0．05），与ROSl、人表皮生长因子受体2、总EGFR、间变性淋巴瘤激酶和磷酸化蛋白激酶B（Ser473）的表达均无关（均p〉0．05）。P13Kpllool的表达与p53的突变无关（P〉0．05）。结论P13Kp110α高表达与不吸烟肺腺癌患者的发生密切相关，EGFR基因突变和MET蛋白过表达可能是肺癌P13Kp110α高表达的重要原因，P13Kp110α高表达可能通过不同于经典P13K通路的途径抑制肿瘤细胞增殖，P13Kpl10α高表达预示肺癌患者的预后较好。
Objective To investigate the clinical significance and mechanism of upregulation of phosphoinositide 3-kinase p110a（PI3Kp110a）in non-small cell hmg carcinoma （NSCLC）. Methods Expressions of PI3Kp110α and other components in PI3K signaling pathway （including phospho-Akt （p-Akt, Ser 473）, MET, ROS1, HER-2, ALK, total EGFR and mutant EGFR） and p53 （the transcription factor of PIK3CA） mutation in NSCLC were detected by immunohistochemistry. The relationships between PI3Kpll0ct expression and clinicopathological characteristics, expressions of other proteins in PI3K pathway and p53 mutation were analyzed. Results In 170 NSCLC patients, 72 cases （42.4%） showed lower expression and 98 cases （57. 6%） showed higher expression of PI3Kpll0ot. Upregulation of PI3Kpll0ot was not significantly associated with gender, age, T stage and pathologic grade （P〉O.05）. While upregulation of PI3Kp110α was significantly associated with smoking status of patients, pathologic classification, N stage, TNM stage and Ki-67 index （P〈0.05）. Expression of Pl3Kp110et was positively correlated with expressions of MET （P〈0.05） and mutant EGFR （P=0.018） , while not signifieantly related with expressions of p-Akt （Ser473）, HER-2, ALK, ROS1, total EGFR or p53 mutation （P〉0.05）. Conclusions Upregulation of PI3Kp110α is closely related with tumorigenesis of non-smoking lung adenocarcinoma. MET overexpression and EGFR mutation may be crucial to upregulate expression of PI3Kpll0α in NSCLC. Overexpression of PI3Kp110α may inhibit tumor cell proliferation in NSCLC through a different pathway other than classical PI3K pathway. Upregulation of PI3Kp110α may predict favorable prognosis of NSCLC patients.
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2017年第10期737-743,共7页
Chinese Journal of Oncology
