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首页> 外文期刊>BMC Cancer >Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors
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Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors

机译:前列腺癌,癌旁正常出现的前列腺组织和无癌器官供体的前列腺组织中基因表达的差异

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Background Typical high throughput microarrays experiments compare gene expression across two specimen classes – an experimental class and baseline (or comparison) class. The choice of specimen classes is a major factor in the differential gene expression patterns revealed by these experiments. In most studies of prostate cancer, histologically malignant tissue is chosen as the experimental class while normal appearing prostate tissue adjacent to the tumor (adjacent normal) is chosen as the baseline against which comparison is made. However, normal appearing prostate tissue from tumor free organ donors represents an alterative source of baseline tissue for differential expression studies. Methods To examine the effect of using donor normal tissue as opposed to adjacent normal tissue as a baseline for prostate cancer expression studies, we compared, using oligonucleotide microarrays, the expression profiles of primary prostate cancer (tumor), adjacent normal tissue and normal tissue from tumor free donors. Results Statistical analysis using Significance Analysis of Microarrays (SAM) demonstrates the presence of unique gene expression profiles for each of these specimen classes. The tumor v donor expression profile was more extensive that the tumor v adjacent normal profile. The differentially expressed gene lists from tumor v donor, tumor v adjacent normal and adjacent normal v donor comparisons were examined to identify regulated genes. When donors were used as the baseline, similar genes are highly regulated in both tumor and adjacent normal tissue. Significantly, both tumor and adjacent normal tissue exhibit significant up regulation of proliferation related genes including transcription factors, signal transducers and growth regulators compared to donor tissue. These genes were not picked up in a direct comparison of tumor and adjacent normal tissues. Conclusions The up-regulation of these gene types in both tissue types is an unexpected finding and suggests that normal appearing prostate tissue can undergo genetic changes in response to or in expectation of morphologic cancer. A possible field effect surrounding prostate cancers and the implications of these findings for characterizing gene expression changes in prostate tumors are discussed.
机译:背景技术典型的高通量微阵列实验比较两个样本类别(实验类别和基线(或比较)类别)之间的基因表达。标本类别的选择是这些实验揭示的差异基因表达模式的主要因素。在大多数前列腺癌研究中,选择组织学上恶性的组织作为实验类别,同时选择与肿瘤相邻的正常出现的前列腺组织(邻近的正常组织)作为进行比较的基线。然而,来自无肿瘤器官供体的正常出现的前列腺组织代表了差异表达研究的基线组织的替代来源。方法为了检查使用供体正常组织相对于邻近正常组织作为前列腺癌表达研究基准的效果,我们使用寡核苷酸微阵列比较了原发性前列腺癌(肿瘤),邻近正常组织和正常组织的表达谱。无肿瘤的供体。结果使用微阵列重要性分析(SAM)进行的统计分析表明,每种标本类别都存在独特的基因表达谱。肿瘤v供体的表达谱比肿瘤v邻近的正常谱更广泛。检查来自肿瘤v供体,肿瘤v邻近正常人和邻近正常v供体比较的差异表达的基因列表,以鉴定受调控的基因。当将供体用作基线时,在肿瘤和邻近的正常组织中相似的基因都受到高度调节。值得注意的是,与供体组织相比,肿瘤和邻近的正常组织均表现出与转录相关的基因(包括转录因子,信号转导子和生长调节剂)的显着上调。这些基因没有直接比较肿瘤和邻近正常组织的信息。结论两种组织中这些基因类型的上调是一个出乎意料的发现,并表明正常出现的前列腺组织可以响应或预期形态癌而发生遗传变化。讨论了前列腺癌周围的可能场效应以及这些发现对表征前列腺肿瘤中基因表达变化的影响。

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