非小细胞肺癌PI3Kp110β高表达的临床意义及机制

发布时间：2018-04-28 14:14

本文选题：肺肿瘤 + PIKpβ　；参考：《中国肺癌杂志》2017年12期

【摘要】：背景与目的磷脂酰肌醇-3激酶(phosphatidylinositide 3-kinases,PI3K)通路是细胞内最重要的信号传导通路之一,参与细胞生长、增殖、分化、运动等多项重要功能,其异常活化见于50%-70%的非小细胞肺癌(nonsmall cell lung cancer,NSCLC)。PI3K蛋白作为PI3K通路的枢纽,表达水平的变化直接影响通路的功能状态,与NSCLC的发生、发展和靶向治疗密切相关。本研究旨在探讨PI3K催化亚基p110β在NSCLC中的表达、临床意义及作用机制。方法采用免疫组化法检测170例NSCLC中p110β和PI3K通路其他蛋白的表达,分析p110β的表达与患者临床病理特征的关系,与PI3K通路其他蛋白表达的关系。结果 p110β在NSCLC的高表达率为41.8%。其表达水平与Ki67计数呈正相关(P=0.040),在腺癌和鳞状细胞癌间、不同性别、年龄、吸烟状况分组间以及不同T分期、N分期、TNM分期和病理学分级间差异均无统计学意义(P0.05)。p110β的高表达与EGFR突变呈负相关(P=0.022),与PTEN表达缺失呈正相关(P0.001),与ROS1、野生型EGFR、HER2、ALK和p-Akt(Ser473)的表达均无明显关系(P0.05)。结论 p110β高表达在NSCLC是一频发事件;与PTEN缺失密切相关,是PTEN缺失肿瘤生存和进展的关键;可导致肿瘤增殖指数升高,但却与磷酸化Akt无关。PIK3CB突变不是p110β高表达的主要原因;各类受体酪氨酸激酶(receptor tyrosine kinases,RTKs)异常均未显示导致癌组织p110β表达增高的能力,而且,EGFR突变者p110β的表达反而低于EGFR野生型。
[Abstract]:Background & objective phosphatidylinositide 3-kinasestid PI3K pathway is one of the most important signal transduction pathways in cells. It is involved in many important functions such as cell growth, proliferation, differentiation and movement. Its abnormal activation was found in 50% -70% of non-small cell lung cancer.PI3K protein as the hub of PI3K pathway. The change of expression level directly affected the functional state of the pathway, and was closely related to the occurrence, development and targeted therapy of NSCLC. The purpose of this study was to investigate the expression, clinical significance and mechanism of PI3K catalytic subunit p110 尾 in NSCLC. Methods Immunohistochemical method was used to detect the expression of p110 尾 and other proteins in PI3K pathway in 170 cases of NSCLC. The relationship between the expression of p110 尾 and clinicopathological features and the expression of other proteins in PI3K pathway was analyzed. Results the high expression rate of p110 尾 in NSCLC was 41.8%. There was a positive correlation between the expression level and Ki67 count (P = 0.040), and between adenocarcinoma and squamous cell carcinoma (SCC), there were different sex and age. There was no significant difference between smoking status groups and between different T stage and N stage, TNM stage and pathological grade. The high expression of P0.05U. P110 尾 was negatively correlated with EGFR mutation, positively correlated with PTEN deletion (P0.001, ROS1, wild type EGFR HER2ALK and p-AktSer473). There was no significant relationship between the expression of P0.05 and P0.05. Conclusion the high expression of p110 尾 in NSCLC is a frequent event, which is closely related to PTEN deletion and is the key to the survival and progression of PTEN deletion, which may lead to the increase of tumor proliferation index, but not to the phosphorylation of Akt. PIK3CB mutation is not the main cause of p110 尾 overexpression. The abnormal expression of tyrosine kinasesserine receptor (tyrosine kinasestir) did not show the ability to increase the expression of p110 尾 in cancer tissues, and the expression of p110 尾 in the mutant was lower than that in the wild type of EGFR.
【作者单位】：北京大学第一医院病理科;
【分类号】：R734.2

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