Center for Systems Biology, Soochow University, No. 1. Shizi Street, Suzhou 215006, China.
Comput Biol Chem. 2011 Jun;35(3):151-8. doi: 10.1016/j.compbiolchem.2011.04.003. Epub 2011 Apr 27.
The development and diverse application of microarray and next generation sequencing technologies has made the meta-analysis widely used in expression data analysis. Although it is commonly accepted that pathway, network and systemic level approaches are more reproducible than reductionism analyses, the meta-analysis of prostate cancer associated molecular signatures at the pathway level remains unexplored. In this article, we performed a meta-analysis of 10 prostate cancer microarray expression datasets to identify the common signatures at both the gene and pathway levels. As the enrichment analysis result of GeneGo's database and KEGG database, 97.8% and 66.7% of the signatures show higher similarity at pathway level than that at gene level, respectively. Analysis by using gene set enrichment analysis (GSEA) method also supported the hypothesis. Further analysis of PubMed citations verified that 207 out of 490 (42%) pathways from GeneGo and 48 out of 74 (65%) pathways from KEGG were related to prostate cancer. An overlap of 15 enriched pathways was observed in at least eight datasets. Eight of these pathways were first described as being associated with prostate cancer. In particular, endothelin-1/EDNRA transactivation of the EGFR pathway was found to be overlapped in nine datasets. The putative novel prostate cancer related pathways identified in this paper were indirectly supported by PubMed citations and would provide essential information for further development of network biomarkers and individualized therapy strategy for prostate cancer.
微阵列和下一代测序技术的发展和多样化应用使得荟萃分析广泛应用于表达数据分析。尽管人们普遍认为通路、网络和系统水平的方法比还原分析更具可重复性，但前列腺癌相关分子特征的通路水平荟萃分析仍未得到探索。在本文中，我们对 10 个前列腺癌微阵列表达数据集进行了荟萃分析，以确定基因和通路水平的共同特征。作为 GeneGo 的数据库和 KEGG 数据库的富集分析结果，分别有 97.8%和 66.7%的特征在通路水平上的相似度高于基因水平。使用基因集富集分析（GSEA）方法的分析也支持了这一假设。对 PubMed 引文的进一步分析验证了 GeneGo 中的 490 条通路中有 207 条（42%），KEGG 中有 74 条通路中有 48 条（65%）与前列腺癌有关。至少在八个数据集中观察到 15 个富集通路的重叠。其中 8 个通路首次被描述与前列腺癌有关。特别是，EGFR 通路中的内皮素-1/EDNRA 对 EGFR 通路的转激活在九个数据集中被发现存在重叠。本文中鉴定的假定的新的前列腺癌相关通路被 PubMed 引文间接支持，并将为网络生物标志物和前列腺癌个体化治疗策略的进一步发展提供重要信息。
