Abstract
Purpose: The molecular, 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 FA in cancer patients remains largely unknown. The present study was comprehensively to examine association of PDPK FA expression with poor prognosis of aggressive cancer patients. Patients and Methods: PDPK FA expression in the resected tumors of 134 hepatocellular carcinoma (HCC) patients, 150 cholangiocarcinoma (CC) patients, and 146 gastric cancer (GC) patients was analyzed by immunohistochemistry. Highly condensed cytoplasmic and nuclear PDPK FA associated with tumor cells was used as the major scoring parameter for positive PDPK FA expression. Survival analysis was used to analyze the data. Results: The frequency of positive PDPK FA expression was 68% (91/134) in HCC, 67% (100/150) in CC, and 58% (84/134) in GC, respectively. Patients with positive PDPK FA showed poorer disease-free survival (DFS) and overall survival (OS) (P<0.001 for both). Cox multivariate regression analysis further established PDPK FA as the strongest independent prognosticator for progression and patient survival of HCC (HR 2.878, 95% CI 1.634-5.067 for DFS and HR 5.035, 95% CI 2.137-11.866 for OS, P<0.001), CC (HR 3.386, 95% CI 1.806-6.348 for OS, P<0.001), and GC (HR 6.84, 95% CI 3.43-13.65 for DFS and HR 5.36, 95% CI 2.61-10.98 for OS, P<0.001). Overexpression of PDPK FA was also a particularly unfavorable maker in the combination analysis on the survival data and could resolve the prognostic uncertainties of the early stage patients. Conclusion: In consistence with its essential role in the development of highly malignant phenotypes, the present study establishes the potential prognostic role of PDPK FA in surgically resected primary HCC, CC and GC. PDPK FA is a common novel molecule for prediction of cancer progression and patient survival. Taken together, PDPK FA represents a new modifiable signal transducing target for prognostic prediction and adjuvant treatment of patients with aggressive cancers after surgical resection.