Department of Pathology, Seoul National University Bundang Hospital, 173-82 Gumiro, Bundang-gu, Seongnam 463-707, Gyeonggi-do, Republic of Korea.
Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-Ro 43-Gil, Songpa-Gu, 138-736 Seoul, Republic of Korea.
Lung Cancer. 2015 Jul;89(1):13-8. doi: 10.1016/j.lungcan.2015.04.003. Epub 2015 Apr 14.
Dysregulation of mammalian target of rapamycin (mTOR) pathway has been linked with malignant tumorigenesis. This study explored the expression profiles of proteins involved in the mTOR pathway and their relationships with clinicopathologic characteristics in stage-I non-small-cell lung carcinoma (NSCLC).
The protein expression profiles of PTEN, p-Akt, p-mTOR, p-S6, and eIF4E were examined using immunohistochemical staining and tissue microarray method in 408 patients with stage-I NSCLC (250 adenocarcinomas [ADC] and 158 squamous cell carcinomas).
Retained PTEN expression (P<0.001), p-mTOR expression (P<0.001), and p-S6 expression (P=0.007) were associated with ADC histology. Expression of PTEN (P=0.001), p-Akt (P=0.005), p-mTOR (P=0.007), p-S6 (P<0.001) were correlated with lower pathologic T stage. PTEN loss was correlated with male gender and smoking history and p-mTOR expression was inversely correlated with these factors (P<0.001). Subgroup analysis of ADCs indicated that male gender, high pT stage, lymphovascular invasion, and PTEN loss were poor prognostic factors. Multivariate analysis revealed that the PTEN(-)/p-Akt(+)/p-mTOR(+) combination more effectively determined the prognosis of ADC (hazard ratio=2.2, P=0.004) than PTEN alone.
Activation of the mTOR pathway in early-stage ADCs suggests a significant role for the mTOR axis in early carcinogenesis. The combination of PTEN(-)/p-Akt(+)/p-mTOR(+) expression was correlated with poor overall survival in patients with stage-I lung ADC.
哺乳动物雷帕霉素靶蛋白（mTOR）通路的失调与恶性肿瘤发生有关。本研究探讨了 mTOR 通路相关蛋白的表达谱及其与 I 期非小细胞肺癌（NSCLC）临床病理特征的关系。
采用免疫组织化学染色和组织微阵列方法检测 408 例 I 期 NSCLC 患者（250 例腺癌[ADC]和 158 例鳞状细胞癌）中 PTEN、p-Akt、p-mTOR、p-S6 和 eIF4E 的蛋白表达谱。
保留的 PTEN 表达（P<0.001）、p-mTOR 表达（P<0.001）和 p-S6 表达（P=0.007）与 ADC 组织学相关。PTEN（P=0.001）、p-Akt（P=0.005）、p-mTOR（P=0.007）和 p-S6（P<0.001）的表达与较低的病理 T 分期相关。PTEN 缺失与男性和吸烟史相关，p-mTOR 表达与这些因素呈负相关（P<0.001）。ADC 的亚组分析表明，男性、高 pT 分期、血管淋巴管侵犯和 PTEN 缺失是不良预后因素。多因素分析显示，PTEN（-）/p-Akt（+）/p-mTOR（+）联合较单独 PTEN 更能有效判断 ADC 的预后（危险比=2.2，P=0.004）。
早期 ADC 中 mTOR 通路的激活表明 mTOR 轴在早期癌变中起重要作用。PTEN（-）/p-Akt（+）/p-mTOR（+）表达的组合与 I 期肺 ADC 患者的总生存期不良相关。
