Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process.
Gene expression profiles of prostate cancer reveal involvement of multiple molecular pathways in the metastatic process.
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前列腺癌的基因表达谱揭示了多个分子途径在转移过程中的参与。
DOI：
10.1186/1471-2407-7-64
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发表时间：
2007-04-12
期刊：
影响因子：
3.8
通讯作者：
Monzon, Federico A.
中科院分区：
文献类型：
--
作者：
Chandran, Uma R.;Ma, Changqing;Dhir, Rajiv;Bisceglia, Michelle;Lyons-Weiler, Maureen;Liang, Wenjing;Michalopoulos, George;Becich, Michael;Monzon, Federico A.
前列腺癌的特征在于临床过程中的异质性，其通常与肿瘤的形态学特征无关。转移反映了前列腺癌最不利的结果，迄今为止，没有可靠的形态学特征或血清生物标志物可以可靠地预测哪些患者发生转移性疾病的风险较高。了解转移性和器官局限性原发性肿瘤的生物学差异对于开发新的预后标志物和治疗靶点至关重要。我们使用Affyphin寡核苷酸阵列分析了从4名患者和先前发表的64个原发性前列腺肿瘤样本的数据集获得的24个雄激素消融抗性转移样本的基因表达谱。在去除可能无信息的基质基因后分析差异基因表达，解决原发性和转移性肿瘤之间细胞内容物的差异。转移性样品在表达上是高度异质性的;然而，差异表达分析显示，在每个具有转移的患者中，415个基因上调，364个基因下调至少2倍。转移性样品的表达谱揭示了一组独特的基因表达的变化，这些基因代表雄激素消融相关途径和其他转移相关基因网络，如细胞粘附、骨重塑和细胞周期。差异表达的基因包括代谢酶、转录因子如叉头盒M1（FoxM 1）和细胞粘附分子如骨桥蛋白（SPP 1）。我们假设这些基因在转移性疾病的生物学中起作用，并且它们代表了前列腺癌的潜在治疗靶点。
Prostate cancer is characterized by heterogeneity in the clinical course that often does not correlate with morphologic features of the tumor. Metastasis reflects the most adverse outcome of prostate cancer, and to date there are no reliable morphologic features or serum biomarkers that can reliably predict which patients are at higher risk of developing metastatic disease. Understanding the differences in the biology of metastatic and organ confined primary tumors is essential for developing new prognostic markers and therapeutic targets. Using Affymetrix oligonucleotide arrays, we analyzed gene expression profiles of 24 androgen-ablation resistant metastatic samples obtained from 4 patients and a previously published dataset of 64 primary prostate tumor samples. Differential gene expression was analyzed after removing potentially uninformative stromal genes, addressing the differences in cellular content between primary and metastatic tumors. The metastatic samples are highly heterogenous in expression; however, differential expression analysis shows that 415 genes are upregulated and 364 genes are downregulated at least 2 fold in every patient with metastasis. The expression profile of metastatic samples reveals changes in expression of a unique set of genes representing both the androgen ablation related pathways and other metastasis related gene networks such as cell adhesion, bone remodelling and cell cycle. The differentially expressed genes include metabolic enzymes, transcription factors such as Forkhead Box M1 (FoxM1) and cell adhesion molecules such as Osteopontin (SPP1). We hypothesize that these genes have a role in the biology of metastatic disease and that they represent potential therapeutic targets for prostate cancer.
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影响因子：
82.9
作者：
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通讯作者：
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