College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.
Department of immunology, Harbin Medical University, Harbin, Heilongjiang, China.
PLoS One. 2013 Dec 26;8(12):e83495. doi: 10.1371/journal.pone.0083495. eCollection 2013.
Accumulating evidence shows a tight link between inflammation and cancer. However, comprehensive identification of pivotal transcription factors (i.e., core TFs) mediating the dysregulated links remains challenging, mainly due to a lack of samples that can effectively reflect the connections between inflammation and tumorigenesis. Here, we constructed a series of TF-mediated regulatory networks from a large compendium of expression profiling of normal colonic tissues, inflammatory bowel diseases (IBDs) and colorectal cancer (CRC), which contains 1201 samples in total, and then proposed a network-based approach to characterize potential links bridging inflammation and cancer. For this purpose, we computed significantly dysregulated relationships between inflammation and their linked cancer networks, and then 24 core TFs with their dysregulated genes were identified. Collectively, our approach provides us with quite important insight into inflammation-associated tumorigenesis in colorectal cancer, which could also be applied to identify functionally dysregulated relationships mediating the links between other different disease phenotypes.
越来越多的证据表明炎症与癌症之间存在紧密联系。然而,全面鉴定介导失调联系的关键转录因子(即核心 TF)仍然具有挑战性,主要是因为缺乏能够有效反映炎症与肿瘤发生之间联系的样本。在这里,我们从一个包含总共 1201 个样本的正常结肠组织、炎症性肠病 (IBD) 和结直肠癌 (CRC) 的表达谱大型汇编中构建了一系列由 TF 介导的调控网络,然后提出了一种基于网络的方法来描述炎症和癌症之间潜在的联系。为此,我们计算了炎症与其相关癌症网络之间显著失调的关系,然后确定了 24 个核心 TF 及其失调基因。总的来说,我们的方法为结直肠癌中炎症相关肿瘤发生提供了重要的见解,也可用于鉴定介导其他不同疾病表型之间联系的功能失调关系。