Proline-Directed Protein Kinase FAIs a Powerful and Independent Prognostic Predictor for Progression and Patient Survival of Hepatocellular Carcinoma

Abstract

PurposeMolecular, cellular, and animal studies have established that overexpressed proline-directed protein kinase FA(PDPK FA) is essential for the development of tumorigenesis, invasion, and metastasis of human cancer cells. However, the prognostic role of PDPK FAin cancer patients remains largely unknown. In this study, association of PDPK FAexpression with poor prognosis of hepatocellular carcinoma (HCC) patients was examined.Patients and MethodsPDPK FAexpression in the resected tumors of 134 HCC patients (112 men and 22 women) with ages ranging from 33 to 83 years (mean, 55 years) was analyzed by immunohistochemistry. Highly condensed cytoplasmic and nuclear PDPK FAassociated with tumor cells was used as the major scoring parameter for positive PDPK FAexpression.ResultsApproximately 68% of the patients (91 of 134) exhibited positive PDPK FAexpression. Patients with positive PDPK FAshowed poorer disease-free survival and overall survival (P < .001). Cox multivariate regression analysis further established PDPK FAas the strongest independent prognosticator for progression and patient survival of HCC (hazard ratio [HR], 2.878; 95% CI, 1.634 to 5.067 for disease-free survival; and HR, 5.035; 95% CI, 2.137 to 11.866 for overall survival; P < .001).ConclusionConsistent with PDPK FA’s essential role in the development of highly malignant phenotypes, the present study establishes the potential prognostic role of PDPK FAin progression and patient survival of surgically resected primary HCC. Taken together, PDPK FArepresents a new modifiable signal-transducing target for prognostic prediction and adjuvant treatment of patients with aggressive HCC after hepatic resection.