PKM2 在肺腺癌中的预后价值及其与肿瘤细胞 PD-L1 的相关性。
The prognostic value of PKM2 and its correlation with tumour cell PD-L1 in lung adenocarcinoma.
机构信息
Department of Thoracic Surgery, Medical College of Nanchang University, Nanchang, 330006, China.
Department of Thoracic Surgery, Jiangxi Cancer Hospital, No. 519 Beijing East Road, Nanchang, 330006, China.
出版信息
BMC Cancer. 2019 Mar 29;19(1):289. doi: 10.1186/s12885-019-5519-2.
BACKGROUND
The prognostic value of PKM2 and its correlation with tumour cell PD-L1 in lung adenocarcinoma (LUAD) is unclear.
METHODS
A total of 506 lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) dataset and 173 LUAD tumour tissues from Jiangxi Cancer Hospital were used to analyse the correlation between PKM2 and PD-L1 expression. We further established a stable LUAD cell line with PKM2 knockdown and confirmed the association via Western blotting and flow cytometry analysis. Moreover, the prognostic values of PKM2 and PD-L1 were evaluated by the Kaplan-Meier method and Cox proportional hazards models.
RESULTS
Based on the above two large cohorts, we found that PKM2 was significantly positively associated with PD-L1 expression (r = 0.132, P = 0.003 and r = 0.287, P < 0.001, respectively). Subsequently, we found that PKM2 knockdown substantially inhibited PD-L1 expression in the A549 LUAD cell line. Moreover, survival analysis showed that higher expression of PKM2 was correlated with significantly shorter overall survival (OS) and disease-free survival (DFS) in lung adenocarcinoma patients (P < 0.001 and P = 0.050, respectively). Subgroup analysis showed that lung adenocarcinoma patients who expressed high PKM2 and PD-L1 levels experienced the poorest OS and DFS. Additionally, multivariate analysis suggested that high PKM2 and PD-L1 expression was an independent prognostic indicator for worse OS and DFS (HR = 1.462, P < 0.001 and HR = 1.436, P = 0.004, respectively).
CONCLUSIONS
Our results demonstrated that PKM2 regulated PD-L1 expression and was associated with poor outcomes in lung adenocarcinoma patients.
背景
PKM2 的预后价值及其与肺腺癌（LUAD）肿瘤细胞 PD-L1 的相关性尚不清楚。
方法
本研究共纳入了来自癌症基因组图谱（TCGA）数据集的 506 例肺腺癌样本和江西肿瘤医院的 173 例 LUAD 肿瘤组织，分析了 PKM2 与 PD-L1 表达的相关性。我们进一步建立了 PKM2 敲低的稳定 LUAD 细胞系，并通过 Western blot 和流式细胞术分析证实了这种关联。此外，还通过 Kaplan-Meier 方法和 Cox 比例风险模型评估了 PKM2 和 PD-L1 的预后价值。
结果
基于上述两个大队列，我们发现 PKM2 与 PD-L1 表达呈显著正相关（r=0.132，P=0.003 和 r=0.287，P<0.001）。随后，我们发现 PKM2 敲低可显著抑制 A549 LUAD 细胞系中 PD-L1 的表达。此外，生存分析表明，肺腺癌患者中 PKM2 表达水平升高与总生存期（OS）和无病生存期（DFS）显著缩短相关（P<0.001 和 P=0.050）。亚组分析表明，表达高 PKM2 和 PD-L1 水平的肺腺癌患者 OS 和 DFS 最差。此外，多变量分析表明，高 PKM2 和 PD-L1 表达是 OS 和 DFS 较差的独立预后指标（HR=1.462，P<0.001 和 HR=1.436，P=0.004）。
结论
我们的研究结果表明，PKM2 调节 PD-L1 表达，并与肺腺癌患者的不良预后相关。
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