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结直肠癌关键基因和通路的生物信息学分析

Bioinformatics Analysis of Key Genes and Pathways in Colorectal Cancer.

作者信息

Qi Yuewen, Qi Haowen, Liu Zeyuan, He Peiyuan, Li Bingqing

机构信息

1 Department of Gastroenterology, Affiliated Hospital of Chengde Medical College, Chengde, P.R. China.

2 Department of Acupuncture and Massage, Chengde Hospital of Traditional Chinese Medicine, Chengde, P.R. China.

出版信息

J Comput Biol. 2019 Apr;26(4):364-375. doi: 10.1089/cmb.2018.0237. Epub 2019 Feb 27.

DOI:10.1089/cmb.2018.0237
PMID:30810359
Abstract

Colorectal cancer (CRC) is the third most prevalent cancer in the world. Although great progress has been made, the specific molecular mechanism remains unclear. This study aimed to explore the differentially expressed genes (DEGs) and underlying mechanisms of CRC using bioinformatics analysis. In this study, we identified a total of 1353 DEGs in the database of GSE113513, including 715 up- and 638 downregulated genes. Gene ontology analysis results showed that upregulated DEGs were significantly enriched in cell division, cell proliferation, and DNA replication. The downregulated DEGs were enriched in immune response, relation of cell growth and inflammatory response. The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that upregulated DEGs were enriched in cell cycle and p53 signaling pathway, whereas the downregulated DEGs were enriched in drug metabolism, metabolism of xenobiotics by cytochrome P450, and nitrogen metabolism. A total of 124 up-key genes and 35 down-key genes were identified from the protein-protein interaction networks. Furthermore, we identified five up-modules (up-A, up-B, up-C, up-D, and up-E) and three down-modules (d-A, d-B, and d-C) by module analysis. The module up-A was enriched in sister chromatid cohesion, cell division, and mitotic nuclear division. Pathways associated with cell cycle, progesterone-mediated oocyte maturation, oocyte meiosis, and p53 signaling pathway. Whereas the d-A was mainly enriched in G-protein coupled receptor signaling pathway, cell chemotaxis, and chemokine-mediated signaling pathway. The pathways enriched in chemokine signaling pathway, cytokine-cytokine receptor interaction, and alcoholism. These key genes and pathways might be used as molecular targets and diagnostic biomarkers for the treatment of CRC.

摘要

结直肠癌(CRC)是全球第三大常见癌症。尽管已取得巨大进展,但其具体分子机制仍不清楚。本研究旨在通过生物信息学分析探索CRC的差异表达基因(DEG)及其潜在机制。在本研究中,我们在GSE113513数据库中总共鉴定出1353个DEG,其中包括715个上调基因和638个下调基因。基因本体分析结果表明,上调的DEG在细胞分裂、细胞增殖和DNA复制方面显著富集。下调的DEG在免疫反应、细胞生长与炎症反应的关系方面富集。京都基因与基因组百科全书通路分析表明,上调的DEG在细胞周期和p53信号通路中富集,而下调的DEG在药物代谢、细胞色素P450对外源生物的代谢以及氮代谢中富集。从蛋白质-蛋白质相互作用网络中鉴定出总共124个上调关键基因和35个下调关键基因。此外,通过模块分析我们鉴定出五个上调模块(上调-A、上调-B、上调-C、上调-D和上调-E)和三个下调模块(下调-A、下调-B和下调-C)。上调模块-A在姐妹染色单体黏连、细胞分裂和有丝分裂核分裂方面富集。与细胞周期、孕酮介导的卵母细胞成熟、卵母细胞减数分裂和p53信号通路相关的通路。而下调模块-A主要在G蛋白偶联受体信号通路、细胞趋化性和趋化因子介导的信号通路中富集。在趋化因子信号通路、细胞因子-细胞因子受体相互作用和酒精中毒方面富集的通路。这些关键基因和通路可能用作CRC治疗的分子靶点和诊断生物标志物。

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