The prognostic value of PKM2 and its correlation with tumour cell PD-L1 in lung adenocarcinoma
The prognostic value of PKM2 and its correlation with tumour cell PD-L1 in lung adenocarcinoma
复制标题
PKM2在肺腺癌中的预后价值及其与肿瘤细胞PD-L1的相关性
DOI：
10.1186/s12885-019-5519-2
复制
发表时间：
2019-03-29
期刊：
影响因子：
3.8
通讯作者：
Hu, Hao
中科院分区：
文献类型：
--
作者：
Guo, Chang-Ying;Zhu, Qian;Hu, Hao
背景PKM2及其与肿瘤细胞PD-L1在肺腺癌（LUAD）中的预后价值尚不清楚。方法采用癌症基因组图谱（TCGA）数据集的506例肺腺癌样本和江西省肿瘤医院173例LUAD肿瘤组织分析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，并通过蛋白质印迹和流式细胞术分析证实了这种关联。此外，通过Kaplan-Meier法和Cox比例风险模型评估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表达呈显着正相关（r = 0.132，P= 0.003和r = 0.287，P< 0.001，分别）。随后，我们发现 PKM2 敲低显着抑制 A549 LUAD 细胞系中 PD-L1 的表达。此外，生存分析显示，肺腺癌患者中PKM2的较高表达与显着较短的总生存期（OS）和无病生存期（DFS）相关（分别为P< 0.001和P= 0.050）。亚组分析显示，表达高 PKM2 和 PD-L1 水平的肺腺癌患者的 OS 和 DFS 最差。此外，多变量分析表明，PKM2 和 PD-L1 高表达是 OS 和 DFS 较差的独立预后指标（分别为 HR = 1.462，P< 0.001 和 HR = 1.436，P= 0.004）。结论我们的结果表明 PKM2 调节 PD-L1 表达，并与肺部不良预后相关腺癌患者。
BackgroundThe prognostic value of PKM2 and its correlation with tumour cell PD-L1 in lung adenocarcinoma (LUAD) is unclear.MethodsA 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.ResultsBased 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 andP= 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).ConclusionsOur results demonstrated that PKM2 regulated PD-L1 expression and was associated with poor outcomes in lung adenocarcinoma patients.