Originally published as JCO Early Release 10.1200/JCO.2005.03.7499 on June 5 2006

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

Yu-Chen Hsu, Hsiao-Hui Fu, Yung-Ming Jeng, Po-Huang Lee, Shiaw-Der Yang

From the Laboratory of Molecular and Cellular Oncology, Institute of Molecular and Cellular Biology, and Department of Life Science, National Tsing Hua University, Hsinchu; and the Department of Pathology and Surgery, National Taiwan University Hospital, Taipei, Taiwan.

Address reprint requests to Shiaw-Der Yang, PhD, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC; e-mail: lsysd{at}life.nthu.edu.tw

Purpose Molecular, cellular, and animal studies have established that overexpressed proline-directed protein kinase F_A (PDPK F_A) is essential for the development of tumorigenesis, invasion, and metastasis of human cancer cells. However, the prognostic role of PDPK F_A 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 F_A 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 F_A 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 F_A expression. Patients with positive PDPK F_A 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 F_A’s essential role in the development of highly malignant phenotypes, the present study establishes the potential prognostic role of PDPK F_A in progression and patient survival of surgically resected primary HCC. Taken together, PDPK F_A represents a new modifiable signal-transducing target for prognostic prediction and adjuvant treatment of patients with aggressive HCC after hepatic resection.

published online ahead of print at www.jco.org on July 5, 2006.

Supported by Grant No. NSC 93-2314-B-007-001 from the National Science Council of Taiwan.

Y.C.H. and H.H.F. contributed equally to this work.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.

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