Expression of Pregnancy Up-regulated Non-ubiquitous Calmodulin Kinase (PNCK) in Hepatocellular Carcinoma.

ABSTRACT

BACKGROUND/AIM: Pregnancy up-regulated non-ubiquitous calmodulin kinase (PNCK) is a member of calmodulin kinase, and overexpression of PNCK with involvement in carcinogenesis have been reported in HER-2 amplified breast cancer, clear cell renal cell carcinoma and nasopharygeal carcinoma. However, the expression of PNCK and its clinical implication have not been elucidated in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We investigated PNCK expression at both the protein and mRNA level using immunohistochemistry (IHC) and microarray gene expression profiling in HCC tissue samples, and evaluated its association with clinicopathological parameters and their potential prognostic significance. RESULTS: High PNCK protein expression and high PNCK mRNA level was observed in 61.7% and 34.7% of total HCC cases, respectively. PNCK mRNA level was higher in tumor tissues than in background non-tumor tissues, and significantly correlated with protein expression by IHC. High PNCK expression was associated with higher Edmondson grade, intrahepatic metastasis, microvascular invasion and higher AFP levels. Patients with high PNCK expression showed shorter recurrence-free survival and disease-specific survival, and high mRNA expression of PNCK was an independent prognostic factor in disease-specific survival. CONCLUSION: Up-regulation of PNCK expression as well as its association with poor prognosis was demonstrated in HCC. PNCK might be a prognostic biomarker of HCC, and could be a potential candidate therapeutic target.