Microarray analysis of differentially-expressed genes and linker genes associated with the molecular mechanism of colorectal cancer.

Microarray analysis of differentially-expressed genes and linker genes associated with the molecular mechanism of colorectal cancer.
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DOI:
10.3892/ol.2016.5122
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发表时间:
2016-11
期刊:
影响因子:
2.9
通讯作者:
Jiang Y
Jiang Y
中科院分区:
医学4区
文献类型:
--
作者:
Shen X;Yue M;Meng F;Zhu J;Zhu X;Jiang Y

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结直肠癌(CRC)是世界上最常见的恶性肿瘤之一,仍是癌症相关死亡的第三大原因。本研究旨在全面阐明结直肠癌的发病机制,并寻找与肿瘤发生发展相关的基因。微阵列GSE44076、GSE41328和GSE44861数据集从基因表达总库下载,并与荟萃分析整合。使用LIMMA软件包从结直肠癌样本中鉴定差异表达基因(DEG),并与邻近的非肿瘤对照进行比较,然后使用数据库注释、可视化和集成发现在线工具进行功能分析。利用Netbox软件构建了DEGS和连接子基因的蛋白质-蛋白质相互作用(PPI)网络,并挖掘了模块。对具有最大节点数的模块执行功能注释。在荟萃分析汇集数据之后,获得了一个数据集,其中包括涉及11,081个基因的327个样本。在结直肠癌样本和邻近的非癌症对照之间共鉴定出697个deg。在PPI网络中,模块1和模块5包含的节点数最多。模块1中的胶原、I型、α1(COL1A1)、COL1A2和基质金属多肽酶9(MMP9)和模块5中的UGDH6-脱氢酶、乙醛脱氢酶1家族成员A1(ALDH1A1)、脂肪酸结合蛋白4(FABP4)和单甘酯脂肪酶(MGL1)具有高度的连接性。功能分析表明,模块1中的基因参与细胞外基质(ECM)相关功能,模块5中的基因参与代谢相关功能。总体而言,COL1A1、COL1A2、MMP9、UGDH、ALDH1A1、FABP4和MGL1等重要的DEG和连接基因通过调节细胞外基质和细胞代谢在结直肠癌的发生发展中发挥重要作用。
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide and remains the third leading cause of cancer-associated mortality. The present study aimed to fully elucidate the pathogenesis of CRC and identify associated genes in tumor development. Microarray GSE44076, GSE41328 and GSE44861 datasets were downloaded from the Gene Expression Omnibus database and integrated with meta-analysis. Differentially-expressed genes (DEGs) were identified from CRC samples compared with adjacent non-cancerous controls using the Limma package in R, followed by functional analysis using the Database for Annotation, Visualization, and Integrated Discovery online tool. A protein-protein interaction (PPI) network of DEGs and linker genes was constructed using NetBox software and modules were also mined. Functional annotation was performed for modules with a maximum number of nodes. Subsequent to meta-analysis to pool the data, one dataset that included 327 samples involved in 11,081 genes was obtained. A total of 697 DEGs were identified between CRC samples and adjacent non-cancerous controls. In the PPI network, modules 1 and 5 contained the maximum number of nodes. Collagen, type I, α1 (COL1A1), COL1A2 and matrix metallopeptidase 9 (MMP9) in module 1 and UDP-glucose 6-dehydrogenase (UGDH), aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), fatty acid binding protein 4 (FABP4) and monoglyceride lipase (MGLL) in module 5 exhibited a high degree of connectivity. Functional analysis indicated that the genes in module 1 were involved in extracellular matrix (ECM)-associated functions and that the genes in module 5 were involved in metabolism-related functions. Overall, significant DEGs and linker genes, namely COL1A1, COL1A2, MMP9, UGDH, ALDH1A1, FABP4 and MGLL, play a crucial role in the development of CRC via regulating the ECM and cell metabolism.
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