Shen Xingjie, Yue Meng, Meng Fansheng, Zhu Jingyu, Zhu Xiaoyan, Jiang Yakun
Department of Gastroenterology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Department of Pharmacy, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Oncol Lett. 2016 Nov;12(5):3250-3258. doi: 10.3892/ol.2016.5122. Epub 2016 Sep 12.
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 (), and matrix metallopeptidase 9 () in module 1 and UDP-glucose 6-dehydrogenase (), aldehyde dehydrogenase 1 family, member A1 (), fatty acid binding protein 4 () and monoglyceride lipase () 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 , , , , , and , play a crucial role in the development of CRC via regulating the ECM and cell metabolism.
结直肠癌(CRC)是全球最常见的恶性肿瘤之一,仍是癌症相关死亡的第三大主要原因。本研究旨在全面阐明CRC的发病机制,并确定肿瘤发生过程中的相关基因。从基因表达综合数据库下载了微阵列GSE44076、GSE41328和GSE44861数据集,并通过荟萃分析进行整合。使用R语言中的Limma软件包从CRC样本与相邻非癌对照中鉴定差异表达基因(DEG),随后使用在线注释、可视化和综合发现数据库工具进行功能分析。使用NetBox软件构建DEG和连接基因的蛋白质-蛋白质相互作用(PPI)网络,并挖掘模块。对节点数量最多模块进行功能注释。在进行荟萃分析以汇总数据后,获得了一个包含327个样本、涉及11,081个基因的数据集。在CRC样本和相邻非癌对照之间共鉴定出697个DEG。在PPI网络中,模块1和5包含的节点数量最多。模块1中的I型胶原α1()和基质金属蛋白酶9()以及模块5中的UDP-葡萄糖6-脱氢酶()、醛脱氢酶1家族成员A1()、脂肪酸结合蛋白4()和甘油单酯脂肪酶()表现出高度的连通性。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,重要的DEG和连接基因,即、、、、、和,通过调节ECM和细胞代谢在CRC的发生发展中起关键作用。