The discovery of putative urine markers for the specific detection of prostate tumor by integrative mining of public genomic profiles.

The discovery of putative urine markers for the specific detection of prostate tumor by integrative mining of public genomic profiles.
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DOI:
10.1371/journal.pone.0028552
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Yang Y
Yang Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen M;Wang K;Zhang L;Li C;Yang Y

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尿液已成为一种有吸引力的生物流体,可用于前列腺癌 (PCa) 的无创检测。迫切需要发现用于 PCa 临床诊断和预后的候选尿液标志物。各种组学概况的不断增加为识别潜在生物标志物提供了巨大的机会。在这里,我们提出了一种简单而有效的策略,通过从公共数据库中挖掘癌症基因组图谱来获得前列腺肿瘤的候选尿液标记物。前列腺、膀胱和肾脏是细胞物质可以释放到尿液中的三个主要组织。为了识别 PCa 特异性的尿液标志物,首先排除膀胱癌和肾癌外泌体中可能脱落的上调实体。通过基于本体的过滤和进一步评估,导出了 19 个编码尿蛋白实体的精简列表,作为假定的 PCa 标记。其中,我们通过通路富集分析发现了10个与肿瘤细胞生长发育过程密切相关的实体。此外,使用这 10 个实体作为种子,我们构建了蛋白质-蛋白质相互作用 (PPI) 子网络,并建议一些尿液标记物作为监测 PCa 侵袭和进展的首选预后标记物。我们的方法能够发现并优先考虑存在于各种体液中的一系列人类疾病的潜在标记。
Urine has emerged as an attractive biofluid for the noninvasive detection of prostate cancer (PCa). There is a strong imperative to discover candidate urinary markers for the clinical diagnosis and prognosis of PCa. The rising flood of various omics profiles presents immense opportunities for the identification of prospective biomarkers. Here we present a simple and efficient strategy to derive candidate urine markers for prostate tumor by mining cancer genomic profiles from public databases. Prostate, bladder and kidney are three major tissues from which cellular matters could be released into urine. To identify urinary markers specific for PCa, upregulated entities that might be shed in exosomes of bladder cancer and kidney cancer are first excluded. Through the ontology-based filtering and further assessment, a reduced list of 19 entities encoding urinary proteins was derived as putative PCa markers. Among them, we have found 10 entities closely associated with the process of tumor cell growth and development by pathway enrichment analysis. Further, using the 10 entities as seeds, we have constructed a protein-protein interaction (PPI) subnetwork and suggested a few urine markers as preferred prognostic markers to monitor the invasion and progression of PCa. Our approach is amenable to discover and prioritize potential markers present in a variety of body fluids for a spectrum of human diseases.
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