Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China.
Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People's Republic of China.
Sci Rep. 2019 Feb 4;9(1):1324. doi: 10.1038/s41598-018-37285-0.
Protein kinase D2 (PKD2) has been reported to be related with progression and invasion in various cancers. However, its prognostic value and the underlying mechanism in lung cancer remains unclear. Herein we evaluated the expression of PKD2 in lung adenocarcinoma and investigated its relationship with EMT. GSEA, TCGA and K-M plotter database were applied and revealed that high PKD2 expression predicted poor outcome and related with lymph nodes metastasis in lung cancer. IHC and qRT-PCR were performed and found PKD2 was elevated in lung adenocarcinoma and negatively related with OS (p = 0.015), PFS (p = 0.006) and the level of E-cadherin (p = 0.021). Experiment in lung adenocarcinoma cell lines demonstrated up-regulation of PKD2 led to high expression of mesenchymal markers (N-cadherin, vim, mmp9 et al.) and EMT transcription factors(zeb1, twist, snail), and the results were reversed when PKD2 was knocked down. Further investigation showed that abrogation of PKD2 inhibited A549 cell migration, invasion, proliferation and induced cell arrest in G2/M phase. We concluded that high expression of PKD2 was associated with poor prognosis and cancer progression in lung adenocarcinoma patients by promoting EMT.
蛋白激酶 D2（PKD2）已被报道与多种癌症的进展和侵袭有关。然而，其在肺癌中的预后价值和潜在机制尚不清楚。在此，我们评估了 PKD2 在肺腺癌中的表达，并研究了其与 EMT 的关系。GSEA、TCGA 和 K-M plotter 数据库的应用表明，高 PKD2 表达预示着不良预后，并与肺癌的淋巴结转移有关。免疫组化和 qRT-PCR 结果显示，PKD2 在肺腺癌中上调，与 OS（p=0.015）、PFS（p=0.006）和 E-钙黏蛋白水平（p=0.021）呈负相关。在肺腺癌细胞系中的实验表明，上调 PKD2 导致间充质标志物（N-钙黏蛋白、vim、mmp9 等）和 EMT 转录因子（zeb1、twist、snail）的高表达，而当 PKD2 被敲低时，结果则相反。进一步的研究表明，抑制 PKD2 可抑制 A549 细胞的迁移、侵袭、增殖，并诱导细胞在 G2/M 期停滞。我们得出结论，PKD2 的高表达通过促进 EMT 与肺腺癌患者的不良预后和癌症进展相关。
