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Notch信号通路组件:肺腺癌中不同的预后指标

Notch Signaling Components: Diverging Prognostic Indicators in Lung Adenocarcinoma.

作者信息

Liu Zhi-Yan, Wu Tao, Li Qing, Wang Min-Cong, Jing Li, Ruan Zhi-Ping, Yao Yu, Nan Ke-Jun, Guo Hui

机构信息

From the Department of Medical Oncology, the First Affiliated Hospital of Xi'an JiaoTong University (Z-YL, TW, QL, M-CW, LJ, Z-PR, YY, K-JN, HG); and Department of Respiratory Medicine, Xi'an central Hospital (Z-YL), Xi'an, Shaanxi, P.R. China.

出版信息

Medicine (Baltimore). 2016 May;95(20):e3715. doi: 10.1097/MD.0000000000003715.

Abstract

Non-small-cell lung cancer (NSCLC) is a lethal and aggressive malignancy. Currently, the identities of prognostic and predictive makers of NSCLC have not been fully established. Dysregulated Notch signaling has been implicated in many human malignancies, including NSCLC. However, the prognostic value of measuring Notch signaling and the utility of developing Notch-targeted therapies in NSCLC remain inconclusive. The present study investigated the association of individual Notch receptor and ligand levels with lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) prognosis using the Kaplan-Meier plotte database. This online database encompasses 2437 lung cancer samples. Hazard ratios with 95% confidence intervals were calculated. The results showed that higher Notch1, Notch2, JAG1, and DLL1 mRNA expression predicted better overall survival (OS) in lung ADC, but showed no significance in SCC patients. Elevated Notch3, JAG2, and DLL3 mRNA expression was associated with poor OS of ADC patients, but not in SCC patients. There was no association between Notch4 and OS in either lung ADC or SCC patients. In conclusion, the set of Notch1, Notch2, JAG1, DLL1 and that of Notch3, JAG2, DLL3 played opposing prognostic roles in lung ADC patients. Neither set of Notch receptors and ligands was indicative of lung SCC prognosis. Notch signaling could serve as promising marker to predict outcomes in lung ADC patients. The distinct features of lung cancer subtypes and Notch components should be considered when developing future Notch-targeted therapies.

摘要

非小细胞肺癌(NSCLC)是一种致命且侵袭性强的恶性肿瘤。目前,NSCLC的预后和预测标志物尚未完全明确。Notch信号失调与包括NSCLC在内的许多人类恶性肿瘤有关。然而,测量Notch信号的预后价值以及在NSCLC中开发Notch靶向治疗的效用仍无定论。本研究使用Kaplan-Meier绘图数据库调查了个体Notch受体和配体水平与肺腺癌(ADC)和鳞状细胞癌(SCC)预后的相关性。这个在线数据库包含2437个肺癌样本。计算了95%置信区间的风险比。结果显示,较高的Notch1、Notch2、JAG1和DLL1 mRNA表达预测肺ADC患者的总生存期(OS)较好,但在SCC患者中无显著意义。Notch3、JAG2和DLL3 mRNA表达升高与ADC患者的OS较差相关,但在SCC患者中并非如此。在肺ADC或SCC患者中,Notch4与OS均无关联。总之,Notch1、Notch2、JAG1、DLL1组和Notch3、JAG2、DLL3组在肺ADC患者中发挥相反的预后作用。两组Notch受体和配体均不能指示肺SCC的预后。Notch信号可作为预测肺ADC患者预后的有前景的标志物。在开发未来的Notch靶向治疗时,应考虑肺癌亚型和Notch成分的独特特征。

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