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α5-nAChR 和 survivin:肺腺癌中的两个潜在生物学靶点。

α5-nAChR and survivin: Two potential biological targets in lung adenocarcinoma.

机构信息

Research Center of Basic Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.

Department of Medical Laboratory, Weifang Medical University, Weifang, China.

出版信息

J Cell Physiol. 2021 Mar;236(3):1787-1797. doi: 10.1002/jcp.29956. Epub 2020 Jul 28.

Abstract

Recent studies have shown that the overexpression of α5 nicotinic acetylcholine receptor (α5-nAChR) is associated with nicotine-related lung carcinogenesis. Survivin is one of the biomarkers of a worse prognosis for smoking-related lung cancer. The aim of this study is to investigate the association of α5-nAChR, survivin, and clinical outcomes in lung adenocarcinoma (LUAD). We analyzed the expression level and correlation of CHRNA5 (encoding α5-nAChR) and BIRC5 (encoding survivin) in LUAD with The Cancer Genome Atlas data set. The relationship between overall survival (OS) and the expression of CHRNA5 or/and BIRC5 was evaluated by the Kaplan-Meier method and Cox proportional hazards model. Moreover, our results showed that the expression of α5-nAChR mediated survivin expression in lung cancer cells and in lung tumor xenografts. Relationships between the expression of α5-nAChR and/or survivin with clinical-pathological characteristics were analyzed using LUAD tissue samples. The results showed that expression of α5-nAChR was correlated with survivin expression in vitro and in vivo. The group coexpressing α5-nAChR and survivin had a worse prognosis than other subgroups in LUAD (p < .05). In conclusion, ascertaining the expression of both α5-nAChR and survivin provides a better measure of prognosis for LUAD patients. The combined inhibition of α5-nAChR and survivin may be a promising multitargeted gene therapeutic strategy in LUAD diagnosis.

摘要

最近的研究表明,α5 型烟碱型乙酰胆碱受体(α5-nAChR)的过表达与尼古丁相关的肺癌发生有关。Survivin 是与吸烟相关的肺癌预后不良的生物标志物之一。本研究旨在探讨α5-nAChR、Survivin 与肺腺癌(LUAD)临床结局的相关性。我们分析了 CHRNA5(编码α5-nAChR)和 BIRC5(编码 Survivin)在 LUAD 中的表达水平及其相关性与 The Cancer Genome Atlas 数据集。通过 Kaplan-Meier 方法和 Cox 比例风险模型评估 CHRNA5 或/和 BIRC5 表达与总生存期(OS)的关系。此外,我们的结果表明,α5-nAChR 表达在肺癌细胞和肺肿瘤异种移植中调节 Survivin 表达。使用 LUAD 组织样本分析了α5-nAChR 和/或 Survivin 表达与临床病理特征之间的关系。结果表明,α5-nAChR 表达与体外和体内 Survivin 表达相关。在 LUAD 中,共表达α5-nAChR 和 Survivin 的组比其他亚组预后更差(p <.05)。总之,确定α5-nAChR 和 Survivin 的表达提供了 LUAD 患者更好的预后衡量标准。联合抑制α5-nAChR 和 Survivin 可能是 LUAD 诊断中一种有前途的多靶点基因治疗策略。

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