PBK/TOPK expression correlates with mutant p53 and affects patients' prognosis and cell proliferation and viability in lung adenocarcinoma

Hum Pathol. 2015 Feb;46(2):217-24. doi: 10.1016/j.humpath.2014.07.026. Epub 2014 Oct 30.


The PDZ-binding kinase/T-LAK cell-originated protein kinase (PBK/TOPK) is highly expressed in many types of tumors. However, its role in lung adenocarcinoma remains elusive. The aims of this study were to investigate the correlation between PBK/TOPK and mutant p53 in lung adenocarcinoma and to evaluate the effect of PBK/TOPK on cell proliferation and viability. Expression of PBK/TOPK and mutant p53 was detected in 127 cases of lung adenocarcinoma and was examined in the A549, GLC-82, and H358 lung adenocarcinoma cell lines by immunohistochemistry staining and Western blot assay. When PBK/TOPK expression was down-regulated by TOPK-specific siRNA in the A549 and GLC-82 lines, the effects of PBK/TOPK on cell proliferation, viability, and mutant p53 expression were evaluated. Expression of PBK/TOPK correlated positively with mutant p53 in both tumor tissues and cell lines. Kaplan-Meier survival analysis demonstrated that PBK/TOPK, mutant p53, lymph node metastasis, distant metastasis, high TNM stage, and poor tumor differentiation were associated with a poor prognosis. Cox multivariate analysis showed that PBK/TOPK, mutant p53, lymph node metastasis, and distant metastasis could each serve as an independent prognostic factor. After down-regulation of PBK/TOPK in the A549 and GLC-82 cell lines, mutant p53 expression was decreased, and cell proliferation and viability were significantly inhibited. Therefore, our results suggest that PBK/TOPK correlates with mutant p53 and affects cell proliferation and viability as well as prognosis in lung adenocarcinoma.

Keywords: Cancer prognosis; Lung adenocarcinoma; PBK/TOPK; Tumor cell proliferation; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Cycle / physiology
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Cell Proliferation / physiology*
  • Cell Survival
  • Female
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Neoplasm Staging
  • Prognosis
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism


  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Mitogen-Activated Protein Kinase Kinases
  • PDZ-binding kinase