Alisoltani Arghavan, Fallahi Hossein, Ebrahimi Mahdi, Ebrahimi Mansour, Ebrahimie Esmaeil
Department of Plant Breeding and Biotechnology, University of Shahrekord, Shahrekord, Iran.
Department of Biology, School of Sciences, Razi University, Kermanshah, Iran.
PLoS One. 2014 May 5;9(5):e96320. doi: 10.1371/journal.pone.0096320. eCollection 2014.
A novel integrative pipeline is presented for discovery of potential cancer-susceptibility regions (PCSRs) by calculating the number of altered genes at each chromosomal region, using expression microarray datasets of different human cancers (HCs). Our novel approach comprises primarily predicting PCSRs followed by identification of key genes in these regions to obtain potential regions harboring new cancer-associated variants. In addition to finding new cancer causal variants, another advantage in prediction of such risk regions is simultaneous study of different types of genomic variants in line with focusing on specific chromosomal regions. Using this pipeline we extracted numbers of regions with highly altered expression levels in cancer condition. Regulatory networks were also constructed for different types of cancers following the identification of altered mRNA and microRNAs. Interestingly, results showed that GAPDH, LIFR, ZEB2, mir-21, mir-30a, mir-141 and mir-200c, all located at PCSRs, are common altered factors in constructed networks. We found a number of clusters of altered mRNAs and miRNAs on predicted PCSRs (e.g.12p13.31) and their common regulators including KLF4 and SOX10. Large scale prediction of risk regions based on transcriptome data can open a window in comprehensive study of cancer risk factors and the other human diseases.
本文提出了一种新颖的综合流程,通过计算不同人类癌症(HC)的表达微阵列数据集在每个染色体区域的基因改变数量,来发现潜在的癌症易感性区域(PCSR)。我们的新方法主要包括预测PCSR,然后识别这些区域中的关键基因,以获得含有新的癌症相关变体的潜在区域。除了发现新的癌症致病变体之外,预测此类风险区域的另一个优势是,在关注特定染色体区域的同时,能够对不同类型的基因组变体进行同步研究。使用这个流程,我们提取了癌症状态下表达水平高度改变的区域数量。在识别出改变的mRNA和microRNA之后,还针对不同类型的癌症构建了调控网络。有趣的是,结果表明,所有位于PCSR的GAPDH、LIFR、ZEB2、mir-21、mir-30a、mir-141和mir-200c,都是构建网络中常见的改变因素。我们在预测的PCSR(如12p13.31)上发现了许多改变的mRNA和miRNA簇,以及它们的共同调节因子,包括KLF4和SOX10。基于转录组数据对风险区域进行大规模预测,可以为全面研究癌症风险因素和其他人类疾病打开一扇窗口。