Increased KIF15 Expression Predicts a Poor Prognosis in Patients with Lung Adenocarcinoma

Abstract

Background/aims: Lung cancer is the leading cause of cancer-related deaths worldwide. The outcome of patients with non-small cell lung cancer remains poor; the 5-year survival rate for stage IV non-small cell lung cancer is only 1.0%. KIF15 is a tetrameric kinesin spindle motor that has been investigated for its regulation of mitosis. While the roles of kinesin motor proteins in the regulation of mitosis and their potentials as therapeutic targets in pancreatic cancer have been described previously, the role of KIF15 in lung cancer development remains unknown.

Methods: Paired lung carcinoma specimens and matched adjacent normal tissues were used for protein analysis. Clinical data were obtained from medical records. We first examined KIF15 messenger RNA expression in The Cancer Genome Atlas database, and then determined KIF15 protein levels using immunohistochemistry and western blotting. Differences between the groups were analyzed using repeated measures analysis of variance. Overall survival was analyzed using the Kaplan-Meier method. Cell-cycle and proliferation assays were conducted using A549, NCI-H1299, and NCI-H226 cells.

Results: KIF15 was significantly upregulated at both the messenger RNA and protein levels in human lung tumor tissues. In patients with lung adenocarcinoma, KIF15 expression was positively associated with disease stages; high KIF15 expression predicted a poor prognosis. KIF15 knockdown using short hairpin RNA in two human lung adenocarcinoma cell lines induced G1/S phase cell cycle arrest and inhibited cell growth, but there was no effect in human lung squamous cell carcinoma.

Conclusion: Our findings show that KIF15 is involved in lung cancer carcinogenesis. KIF15 could therefore serve as a specific prognostic marker for patients with lung adenocarcinoma.

Keywords: Cell cycle; Cell growth; Clinical outcome; KIF15; Lung cancer.