High PKD2 predicts poor prognosis in lung adenocarcinoma via promoting Epithelial-mesenchymal Transition

Sci Rep. 2019 Feb 4;9(1):1324. doi: 10.1038/s41598-018-37285-0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / pathology
  • Aged
  • Biomarkers, Tumor / genetics*
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Nuclear Proteins / genetics
  • Prognosis*
  • Protein Kinase D2
  • Protein Kinases / genetics*
  • Snail Family Transcription Factors / genetics
  • Twist-Related Protein 1 / genetics
  • Zinc Finger E-box-Binding Homeobox 1 / genetics

Substances

  • Biomarkers, Tumor
  • Nuclear Proteins
  • Protein Kinase D2
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • TWIST1 protein, human
  • Twist-Related Protein 1
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • Protein Kinases