Unfavorable Prognostic Value of Human PEDF Decreased in High-Grade Prostatic Intraepithelial Neoplasia: A Differential Proteomics Approach

Abstract

Background: High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precursor of prostate cancer, but the frequency and timing of epigenetic changes found in prostate carcinogenesis has not been extensively documented. Methods: Here, we performed a differential proteomic profiling study on the serum of HGPIN and prostate cancer patients. Eleven HGPIN patients were enrolled, their serum protein patterns (2D-electrophoresis and mass spectroscopy) were compared with fifteen prostate cancer patients, and the follow-up study was further performed in the HGPIN patients. Results: We described eleven altered protein spots in these two groups, in which pigment epithelium-derived factor (PEDF) was found to be significantly down-regulated in prostate cancer patients, which was further confirmed by ELISA method. In addition, 18.2% (2/11) of the HGPIN revealed strong expression for PEDF, 27.3%(3/11) showed a moderate expression and 54.5% (6/11) a weak PEDF expression in immunohistochemistry study, while in prostatic cancerous cells, 100% patients (15/15) revealed a weak expression for PEDF. The ten months’ follow-up study demonstrated that 2 of 6 HGPIN patients with weakly expressed PEDF were found to have subsequent prostate cancer. Conclusions: our data identified PEDF in HGPIN as a significant predictor of subsequent cancer, suggesting that PEDF implies in prostatic tumorigenesis and may be used to identify the patients with isolated HGPIN who are at high risk for cancer onset in the disease process.