Comparative mRNA and microRNA expression profiling of three genitourinary cancers reveals common hallmarks and cancer-specific molecular events.

Comparative mRNA and microRNA expression profiling of three genitourinary cancers reveals common hallmarks and cancer-specific molecular events.
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三种泌尿生殖系统癌症的 mRNA 和 microRNA 表达谱比较揭示了共同标志和癌症特异性分子事件

DOI:
10.1371/journal.pone.0022570
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Zhang X
Zhang X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li X;Chen J;Hu X;Huang Y;Li Z;Zhou L;Tian Z;Ma H;Wu Z;Chen M;Han Z;Peng Z;Zhao X;Liang C;Wang Y;Sun L;Chen J;Zhao J;Jiang B;Yang H;Gui Y;Cai Z;Zhang X

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使用深度测序技术的全基因组基因表达谱可以推动癌症生物标志物和治疗靶点的发现。这些努力通常限于分析单一类型癌症中mRNA或microRNA(miRNA)的表达特征。方法在这里,我们提供了一个综合分析的全基因组的mRNA和miRNA表达谱的三种不同的泌尿生殖系统癌症:膀胱癌,肾癌和睾丸。主要发现我们的研究结果突出了几个基因和miRNA的一般或癌症特异性作用,这些基因和miRNA可能作为候选癌基因或肿瘤发展的抑制因子。系统水平的进一步比较分析显示,细胞粘附过程、p53信号传导、钙信号传导、ECM受体和细胞周期途径、DNA修复和复制过程以及免疫和炎症反应过程的显著畸变是人类癌症的共同标志。显示睾丸癌特异性失调模式的基因集主要涉及与男性生殖功能相关的过程,并且与细胞迁移相关的多个代谢途径和过程的一般中断分别是肾癌和膀胱癌的特征性分子事件。此外,我们还证明了具有相同组织学起源和具有相似功能的基因的肿瘤倾向于在聚类分析中聚集在一起。通过评估每种miRNA的表达与其靶点之间的相关性,我们确定“关键”miRNA的失调可能导致一种或多种途径或过程的整体畸变。结论系统分析了3种泌尿生殖系统肿瘤的分子表型,同时在miRNA水平上研究了它们的变异。我们的研究结果为未来的研究提供了有价值的来源,并突出了一些有前途的基因,miRNA,途径和过程,可能是有用的诊断或治疗应用。
Background Genome-wide gene expression profile using deep sequencing technologies can drive the discovery of cancer biomarkers and therapeutic targets. Such efforts are often limited to profiling the expression signature of either mRNA or microRNA (miRNA) in a single type of cancer. Methodology Here we provided an integrated analysis of the genome-wide mRNA and miRNA expression profiles of three different genitourinary cancers: carcinomas of the bladder, kidney and testis. Principal Findings Our results highlight the general or cancer-specific roles of several genes and miRNAs that may serve as candidate oncogenes or suppressors of tumor development. Further comparative analyses at the systems level revealed that significant aberrations of the cell adhesion process, p53 signaling, calcium signaling, the ECM-receptor and cell cycle pathways, the DNA repair and replication processes and the immune and inflammatory response processes were the common hallmarks of human cancers. Gene sets showing testicular cancer-specific deregulation patterns were mainly implicated in processes related to male reproductive function, and general disruptions of multiple metabolic pathways and processes related to cell migration were the characteristic molecular events for renal and bladder cancer, respectively. Furthermore, we also demonstrated that tumors with the same histological origins and genes with similar functions tended to group together in a clustering analysis. By assessing the correlation between the expression of each miRNA and its targets, we determined that deregulation of ‘key’ miRNAs may result in the global aberration of one or more pathways or processes as a whole. Conclusions This systematic analysis deciphered the molecular phenotypes of three genitourinary cancers and investigated their variations at the miRNA level simultaneously. Our results provided a valuable source for future studies and highlighted some promising genes, miRNAs, pathways and processes that may be useful for diagnostic or therapeutic applications.
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