An integrated study on TFs and miRNAs in colorectal cancer metastasis and evaluation of three co-regulated candidate genes as prognostic markers
An integrated study on TFs and miRNAs in colorectal cancer metastasis and evaluation of three co-regulated candidate genes as prognostic markers
复制标题
DOI：
10.1016/j.gene.2018.09.003
复制
发表时间：
2018-12-30
期刊：
影响因子：
3.5
通讯作者：
Motalebzadeh, Jamshid
中科院分区：
文献类型：
--
作者：
Eskandari, Elaheh;Mahjoubi, Frouzandeh;Motalebzadeh, Jamshid
癌症中发生的分子改变有可能被认为是癌症生物标志物或靶向治疗，甚至两者兼而有之。在本研究中，我们的目的是阐明转移性结直肠癌的基因调控网络，使用从微阵列获得的数据，以达到最常见的DEG在结直肠癌转移，并找到其可能的调控机制，通过DETF和DEmiR。在这方面，采用七个微阵列数据集来评估结直肠癌转移中最重要的DEG、DETF和DEmiR。在此基础上，构建了基于DETF和DEmiR的GRN。ARACNE算法也被用来构建一个精确的GRN。对GRN进行结构分析，然后通过真实的qRT-PCR对50例结直肠癌患者中的两种DETF（LEF 1和ETV 4）和一种不太知名的DEG（FABP 6）进行定量。构建的GRN强调了一些DETF和DEmiR在结直肠癌转移中的重要性。有趣的是，通过qRT-PCR对三个候选基因（LEF1、ETV4和FABP6）进行的基因表达分析表明，这三个基因在肿瘤样品中共表达，并且与结直肠癌的转移显著相关。因此，我们的实验结果证明了我们的综合数据分析和系统生物学结果的一部分。综上所述，根据我们的实证研究，我们发现了三个候选基因作为结直肠癌转移的有效预后因子的重要性。我们对基因调控机制的整体研究揭示了一些基因调控因子（DETF和DEmiR）的重要性及其作为结直肠癌预后因子和/或分子靶向治疗靶点的潜力。
Molecular alterations that occur in cancer have the potential to be considered as either cancer biomarkers or targeted therapies or even both. In the presented study, we aimed to elucidate the gene regulatory network of metastatic colorectal cancer using data acquired from microarrays to reach the most common DEGs in colorectal cancer metastasis and find their possible regulatory mechanism by DETFs and DEmiRs. In this regards, seven microarray datasets were employed to assess the most important DEGs, DETFs and DEmiRs in colorectal cancer metastasis. Afterward, GRN based on DETFs and DEmiRs were constructed. Also ARACNE algorithm was used to construct an accurate GRN. GRN was analyzed structurally and then, two DETFs (LEF1 and ETV4) and a less-well known DEG (FABP6) by real time qRT-PCR in 50 patients with colorectal cancer were quantified. The constructed GRN highlighted the importance of some DETFs and DEmiRs in colorectal cancer metastasis. Interestingly the gene expression analysis by qRT-PCR on three candidate genes (LEF1, ETV4 and FABP6) indicated that the three genes were co-expressed in tumor samples, and were significantly associated with metastasis in colorectal cancer. Therefore, our experimental results proved a part of our comprehensive data analysis and system biology results. In summary, according to our empirical study we found the importance of three candidate genes as the potent prognostic factors in colorectal cancer metastasis. Also our study in a holistic insight on gene regulatory mechanism revealed the importance of some gene regulatory factors (DETFs and DEmiRs) and their potential as prognostic factors and/or targets in molecular targeted therapies in colorectal cancer.