Proline-directed protein kinase FA is a powerful and independent prognostic predictor for progression and patient survival of hepatocellular carcinoma
Journal
Journal of Clinical Oncology
Journal Volume
24
Journal Issue
23
Pages
3780-3788
Date Issued
2006
Author(s)
Abstract
Purpose: 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. In this study, association of PDPK F A expression with poor prognosis of hepatocellular carcinoma (HCC) patients was examined. Patients and Methods: PDPK FA expression 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 FA associated with tumor cells was used as the major scoring parameter for positive PDPK F A expression. Results: Approximately 68% of the patients (91 of 134) exhibited positive PDPK FA expression. Patients with positive PDPK FA showed poorer disease-free survival and overall survival (P < .001). Cox multivariate regression analysis further established PDPK F A as 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). Conclusion: Consistent with PDPK FA's essential role in the development of highly malignant phenotypes, the present study establishes the potential prognostic role of PDPK FA in progression and patient survival of surgically resected primary HCC Taken together, PDPK FA represents a new modifiable signal-transducing target for prognostic prediction and adjuvant treatment of patients with aggressive HCC after hepatic resection. ? 2006 by American Society of Clinical Oncology.
SDGs
Other Subjects
proline directed protein kinase; proline directed protein kinase f a; unclassified drug; focal adhesion kinase 1; tumor marker; adult; aged; article; cancer growth; cancer patient; cancer survival; controlled study; disease free survival; female; human; immunohistochemistry; liver cell carcinoma; major clinical study; male; priority journal; prognosis; protein expression; analysis of variance; disease course; enzymology; gene expression regulation; liver cell carcinoma; liver tumor; middle aged; prediction and forecasting; proportional hazards model; signal transduction; survival; Adult; Aged; Aged, 80 and over; Analysis of Variance; Carcinoma, Hepatocellular; Disease Progression; Disease-Free Survival; Female; Focal Adhesion Kinase 1; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Liver Neoplasms; Male; Middle Aged; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Signal Transduction; Survival Analysis; Tumor Markers, Biological
Type
journal article