期刊
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
卷 71, 期 5, 页码 1309-1315出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ijrobp.2007.12.010
关键词
protein kinase A RI-alpha; PKA RI-alpha; androgen deprivation; radiotherapy
资金
- NCI NIH HHS [CA 006927, CA 101984-01, CA 21661, R01 CA101984-05, R01 CA101984, CA 32115, P30 CA006927, U10 CA032115, U10 CA021661] Funding Source: Medline
Purpose: The RI-a regulatory subunit of protein kinase A type 1 (PKA) is constitutively overexpressed in human cancer cell lines and is associated with active cell growth and neoplastic transformation. This report examined the association between PKA expression and the endpoints of biochemical failure (BF), local failure (LF), distant metastasis (DM), cause-specific mortality (CSM), and overall mortality in men treated with radiotherapy, with or without short-term androgen deprivation in Radiation Therapy Oncology Group trial 86-10. Methods and Materials: Pretreatment archival diagnostic tissue samples from 80 patients were stained for PKA by immunohistochemical methods from a parent cohort of 456 cases. PKA intensity was scored manually and by image analysis. The Cox proportional hazards model for overall mortality and Fine and Gray's regression models for CSM, DM, LF and BF were then applied to determine the relationship of PKA expression to the endpoints. Results: The pretreatment characteristics of the missing and determined PKA groups were not significantly different. On univariate analyses, a high PKA staining intensity was associated with BF (image analysis, continuous variable,p = 0.022), LF (image analysis, dichotomized variable,p = 0.011), CSM (manual analysis,p = 0.037; image analysis, continuous,p = 0.014), and DM (manual analysis,p = 0.029). On multivariate analyses, the relationships to BF (image analysis, continuous, p = 0.03), LF (image analysis, dichotomized, p = 0.002), and DM remained significant (manual analysis, p = 0.018). In terms of CSM, a trend toward an association was seen (manual analysis, p = 0.08; image analysis, continuous, p = 0.09). Conclusion: PKA overexpression was significantly related to patient outcome and is a potentially useful biomarker for identifying high-risk prostate cancer patients who might benefit from a PKA knockdown strategy. 9 2008 Elsevier Inc.
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