Differences in gene expression in prostate cancer, normal appearing prostate tissue adjacent to cancer and prostate tissue from cancer free organ donors.
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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DOI：
10.1186/1471-2407-5-45
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发表时间：
2005-05-13
期刊：
影响因子：
3.8
通讯作者：
Gilbertson J
中科院分区：
文献类型：
--
作者：
Chandran UR;Dhir R;Ma C;Michalopoulos G;Becich M;Gilbertson J
典型的高通量微阵列实验比较两个样本类别的基因表达-实验类别和基线（或比较）类别。标本类的选择是这些实验揭示的差异基因表达模式的一个主要因素。在大多数前列腺癌的研究中，组织学上的恶性组织被选择为实验类，而与肿瘤相邻的正常表现的前列腺组织（相邻正常）被选择为进行比较的基线。然而，来自无肿瘤器官供体的正常前列腺组织代表了差异表达研究的基线组织的替代来源。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的基线的效果，我们使用寡核苷酸微阵列比较了原发性前列腺癌（肿瘤）、邻近正常组织和来自无肿瘤供体的正常组织的表达谱。使用微阵列显著性分析（SAM）进行的统计分析表明，这些样本类别中的每一个都存在独特的基因表达谱。肿瘤与供体的表达谱比肿瘤与邻近正常谱更广泛。对肿瘤与供体、肿瘤与邻近正常和邻近正常与供体比较的差异表达基因列表进行检查，以鉴定调控基因。当供体被用作基线时，相似的基因在肿瘤和邻近的正常组织中都受到高度调节。值得注意的是，与供体组织相比，肿瘤和邻近的正常组织都表现出增殖相关基因的显著上调，包括转录因子、信号转导因子和生长调节因子。这些基因在肿瘤和邻近正常组织的直接比较中没有被挑选出来。这两种组织类型中这些基因类型的上调是一个意外的发现，表明正常的前列腺组织可以发生遗传变化，以响应或预期形态学癌症。一个可能的场效应周围的前列腺癌和前列腺肿瘤中的基因表达变化的特点，这些研究结果的影响进行了讨论。
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. 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. 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. 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.
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