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

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.