Department of Medical Informatics, Daqing Campus, Harbin Medical University, Daqing 163319, China.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.
Molecules. 2017 Sep 22;22(10):1599. doi: 10.3390/molecules22101599.
Aberrant metabolism is one of the main driving forces in the initiation and development of ESCC. Both genes and metabolites play important roles in metabolic pathways. Integrative pathway analysis of both genes and metabolites will thus help to interpret the underlying biological phenomena. Here, we performed integrative pathway analysis of gene and metabolite profiles by analyzing six gene expression profiles and seven metabolite profiles of ESCC. Multiple known and novel subpathways associated with ESCC, such as 'beta-Alanine metabolism', were identified via the cooperative use of differential genes, differential metabolites, and their positional importance information in pathways. Furthermore, a global ESCC-Related Metabolic (ERM) network was constructed and 31 modules were identified on the basis of clustering analysis in the ERM network. We found that the three modules located just to the center regions of the ERM network-especially the core region of Module_1-primarily consisted of aldehyde dehydrogenase (ALDH) superfamily members, which contributes to the development of ESCC. For Module_4, pyruvate and the genes and metabolites in its adjacent region were clustered together, and formed a core region within the module. Several prognostic genes, including GPT, ALDH1B1, ABAT, WBSCR22 and MDH1, appeared in the three center modules of the network, suggesting that they can become potentially prognostic markers in ESCC.
代谢异常是 ESCC 发生和发展的主要驱动因素之一。基因和代谢物在代谢途径中都起着重要作用。因此，对基因和代谢物的综合途径分析将有助于解释潜在的生物学现象。在这里，我们通过分析 6 个 ESCC 的基因表达谱和 7 个代谢谱，对基因和代谢物谱进行了综合途径分析。通过协同使用差异基因、差异代谢物及其在途径中的位置重要性信息，确定了与 ESCC 相关的多个已知和新的亚途径，如“β-丙氨酸代谢”。此外，还构建了一个全局 ESCC 相关代谢 (ERM) 网络，并在 ERM 网络的聚类分析基础上鉴定了 31 个模块。我们发现，ERM 网络中位于中心区域的三个模块——特别是模块 1 的核心区域——主要由醛脱氢酶 (ALDH) 超家族成员组成，这有助于 ESCC 的发展。对于模块 4，丙酮酸及其相邻区域的基因和代谢物聚集在一起，并在该模块内形成一个核心区域。网络的三个中心模块中出现了几个预后基因，包括 GPT、ALDH1B1、ABAT、WBSCR22 和 MDH1，表明它们可能成为 ESCC 的潜在预后标志物。
