捕获显微切割及基因芯片技术对前列腺病变基因表达谱的分析

Microdissection and Microarray Analysisof Prostatic Intraepithelial neoplasia and Prostate Carcinoma

目的:应用基因芯片技术,分析前列腺上皮内瘤变(PIN)及前列腺癌的基因表达谱,并将其与良性增生(BPH)前列腺组织的基因表达谱进行对比,探讨与前列腺癌的发生、发展密切相关的基因,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5例良性标本,6例PIN以及5例前列腺癌标本;采用激光捕获显微切割技术,分别得到了3组纯的上皮细胞群。结果:3组间基因表达谱存在非常显著的差异。与良性增生及前列腺癌相比,PIN有其独特的基因表达谱。有些基因的表达强度在从良性增生到PIN再到癌的过程中,呈逐渐改变的趋势,表现为逐渐上调或逐渐下调。结论:基因表达谱中显著改变的特异性基因可以将PIN和BPH及前列腺癌中区分开来;在从良性增生到PIN再到癌的过程中,有些基因的改变呈渐进性发展。

Objective： To identify mRNA profiles in microdissected PIN and prostate carcinoma by microarray analysis and to compare mRNA expression patterns between benign hyperplasia, PIN and tumorous epithelia in order to get insight into the carcinogenesis and development of prostate cancer and obtain biomarkers for PIN and prostate carcinoma. Methods： Gene expression profiles were generated from 5 benign hyperplasia, 6 PIN and 5 prostate cancer. Affymetrix Human Genome U133 A （HG-U133A） microarrays were used in this study. Laser capture microdissection （LCM） was performed to procure pure epithelial cell populations. Results： 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 hyperplasia and carcinoma. Notably, many genes were found gradually modulated （up--regulation or down-regulation） in the transition of benign hyperplasia to PIN to prostate cancer. Conclusion： The results show that gene expression separates benign hyperplasia, PIN and prostate cancer by both significant increases and decreases in expression of specific genes. Gradually modulated genes were observed in the reansition of BPH to PIN to carcionma.