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 progression and patient survival of non-small cell lung cancer (NSCLC). PATIENTS and METHODS: PDPK FA expression in the resective tumors of 156 NSCLC patients was analyzed by immunohistochemistry. Highly condensed 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 51% (80/156) in NSCLC. 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 NSCLC (HR 5.438, 95% CI 3.436-8.608 for DFS, P<0.001; HR 8.106, 95% CI 4.741-13.859 for OS, P<0.001). In the combination analysis with independent prognostic factor on the survival data, PDPK FA further appeared to play a determinant, instructional and predominant role superior to the current powerful TNM staging system in prognostic prediction. At last, the logistic analysis showed that established PDPK FA is a very powerful prognostic indicator of response to adjuvant therapy in the NSCLC patients (OR 11.190, 95% CI 2.701-46.367, P=0.001). CONCLUSION: In consistence with its multisubstrate/multifunctional PDPK nature essential for the development of highly malignant phenotypes, the present human study indicates that PDPK FA is a new signal transducing molecule for prediction of cancer progression and response to adjuvant therapy. Together with the previous molecular, cellular and animal studies, the thesis establishes PDPK FA as a new promising target for the strategic development of reliable and accessible prognostic and therapeutic modalities for more efficacious treatment of NSCLC.