Qingyi Zhu, Lin Yuan, Junhong Wang, Jian Su, Weizhou Huang, Long Ma, Zeyu Sun, Xiaojian Gu
Department of Urology, Jiangsu Province Hospital of TCM, Nanjing, PR China.
Cancer Invest. 2009 Aug;27(7):794-801. doi: 10.1080/07357900802175617.
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.
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.
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.
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.
高级别前列腺上皮内瘤变（HGPIN）是前列腺癌最可能的前驱病变，但前列腺癌发生过程中表观遗传变化的频率和时间尚未得到广泛记录。
在此，我们对HGPIN患者和前列腺癌患者的血清进行了差异蛋白质组学分析研究。纳入了11例HGPIN患者，将他们的血清蛋白质图谱（二维电泳和质谱分析）与15例前列腺癌患者进行比较，并对HGPIN患者进行了随访研究。
我们描述了这两组中11个改变的蛋白斑点，其中发现色素上皮衍生因子（PEDF）在前列腺癌患者中显著下调，这通过酶联免疫吸附测定法得到进一步证实。此外，在免疫组织化学研究中，18.2%（2/11）的HGPIN显示PEDF强表达，27.3%（3/11）显示中度表达，54.5%（6/11）显示弱PEDF表达，而在前列腺癌细胞中，100%的患者（15/15）显示PEDF弱表达。为期10个月的随访研究表明，6例PEDF弱表达的HGPIN患者中有2例随后发生了前列腺癌。
我们的数据确定HGPIN中的PEDF是后续癌症的重要预测指标，表明PEDF参与前列腺肿瘤发生，并且可用于识别在疾病过程中患癌风险高的孤立性HGPIN患者。
