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首页> 外文期刊>BMC Medical Genomics >Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data
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Candidate pathways and genes for prostate cancer: a meta-analysis of gene expression data

机译：前列腺癌的候选途径和基因：基因表达数据的荟萃分析

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Backgound The genetic mechanisms of prostate tumorigenesis remain poorly understood, but with the advent of gene expression array capabilities, we can now produce a large amount of data that can be used to explore the molecular and genetic mechanisms of prostate tumorigenesis. Methods We conducted a meta-analysis of gene expression data from 18 gene array datasets targeting transition from normal to localized prostate cancer and from localized to metastatic prostate cancer. We functionally annotated the top 500 differentially expressed genes and identified several candidate pathways associated with prostate tumorigeneses. Results We found the top differentially expressed genes to be clustered in pathways involving integrin-based cell adhesion: integrin signaling, the actin cytoskeleton, cell death, and cell motility pathways. We also found integrins themselves to be downregulated in the transition from normal prostate tissue to primary localized prostate cancer. Based on the results of this study, we developed a collagen hypothesis of prostate tumorigenesis. According to this hypothesis, the initiating event in prostate tumorigenesis is the age-related decrease in the expression of collagen genes and other genes encoding integrin ligands. This concomitant depletion of integrin ligands leads to the accumulation of ligandless integrin and activation of integrin-associated cell death. To escape integrin-associated death, cells suppress the expression of integrins, which in turn alters the actin cytoskeleton, elevates cell motility and proliferation, and disorganizes prostate histology, contributing to the histologic progression of prostate cancer and its increased metastasizing potential. Conclusion The results of this study suggest that prostate tumor progression is associated with the suppression of integrin-based cell adhesion. Suppression of integrin expression driven by integrin-mediated cell death leads to increased cell proliferation and motility and increased tumor malignancy.
机译：背景技术对前列腺肿瘤发生的遗传机制仍然知之甚少，但是随着基因表达阵列功能的出现，我们现在可以产生大量数据，可用于探索前列腺肿瘤发生的分子和遗传机制。方法我们对18个基因阵列数据集中的基因表达数据进行了荟萃分析，目标是从正常前列腺癌向局限性前列腺癌以及从局限性转移至转移性前列腺癌。我们在功能上注释了前500个差异表达的基因，并鉴定了与前列腺癌发生相关的几种候选途径。结果我们发现最主要的差异表达基因聚集在涉及基于整合素的细胞粘附的途径中：整合素信号传导，肌动蛋白细胞骨架，细胞死亡和细胞运动性途径。我们还发现整联蛋白本身在从正常前列腺组织向原发性局部前列腺癌的转变中被下调。基于这项研究的结果，我们提出了前列腺癌发生的胶原假说。根据该假设，前列腺肿瘤发生中的起始事件是与年龄相关的胶原蛋白基因和其他编码整联蛋白配体的基因表达下降。整合素配体的这种耗竭导致无配体整合素的积聚和整合素相关细胞死亡的激活。为了逃避整合素相关的死亡，细胞抑制了整合素的表达，进而改变了肌动蛋白的细胞骨架，提高了细胞的运动性和增殖能力，并使前列腺组织学紊乱，从而促进了前列腺癌的组织学进展及其转移潜力的增加。结论这项研究的结果表明，前列腺肿瘤的进展与整合素基细胞粘附的抑制有关。由整联蛋白介导的细胞死亡驱动的整联蛋白表达的抑制导致细胞增殖和运动性增加以及肿瘤恶性性增加。

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