前列腺上皮内瘤变的基因微阵列分析

目的:通过基因微阵列分析,研究经显微切割后的前列腺上皮内瘤变(PIN)的基因表达谱,并将其与前列腺良性增生(BPH)及前列腺癌的mRNA基因表达谱进行对比,探讨前列腺癌的发生、发展,检测PIN及前列腺癌的肿瘤标志物。方法:采用美国Affymetrix公司的HG-U133A基因芯片,检测了16例人的前列腺组织标本,包括5例良性标本,6例PIN以及5例前列腺癌标本,均为新鲜冰冻组织。为了精确获得上皮细胞基因表达谱,避免周围间质细胞及单核细胞的RNA 对结果的影响,我们采用了激光捕获显微切割技术,分别得到了3组纯的上皮细胞群进行研究。结果:有些基因的表达强度在从良性增生到PIN到癌的转化过程中,呈逐渐改变的趋势,但笔者发现3组间基因表达谱存在非常显著的差异。与BPH及前列腺癌相比,PIN有其独特的基因表达谱。结论:基因表达谱中显著上调及下调的特异性基因,可以将PIN 和BPH及前列腺癌中区分开来;基因微阵列分析也有助于揭示代谢通路及信号转导途径的变化,有利于靶基因治疗。

Microarray analysis of prostatic intraepithelial neoplasia

To identify a mRNA profile in microdissected prostatic intraepithelial neoplasia (PIN) by microarray analysis and to compare mR-NA expression patterns among hyperplastic prostate epithelia, PIN and tumorous epithelia in order to obtain biomarkers for PIN and prostate carcinoma and get insight into the carcinogenesis and development of prostate cancer. Methods: Gene expression profiles were generated from 16 human prostate frozen tissue specimens including 5 hyperplasia, 6 PIN and 5 cancer using microarrays. To obtain precise expression profiles for epithelia and avoid contamination of other cells, laser capture microdissection (LCM) was performed to procure pure epithelial cell populations from cancer, PIN and benign hyperplasia. This approach excluded contribution of RNA from fibromuscular tissue and tumor-infiltrating mononuclear cells to the gene expression profile. Results: Strikingly, clear differences of gene expression patterns were observed among the three groups investigated. A unique mRNA profile was observed in microdissected PIN cells compared to those of other two groups. Many genes were found gradually modulated in the transition of hyperplasia to PIN, to prostate cancer. Conclusion: The results show that gene expression can be used to distinguish benign prostate hyperplasia from PIN and prostate cancer by both significant increase as well as decrease in expression of those specific genes. Analysis of these gene expression profiles can also reveal metabolic or signal trans-duction pathways that might be targeted by new therapeutic strategies.