Application of weighted gene co-expression network analysis to explore the potential diagnostic biomarkers for colorectal cancer

Application of weighted gene co-expression network analysis to explore the potential diagnostic biomarkers for colorectal cancer
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应用加权基因共表达网络分析探索结直肠癌潜在的诊断生物标志物

DOI:
10.3892/mmr.2020.11047
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发表时间:
2020-04
影响因子:
3.4
通讯作者:
Wang Li
Wang Li
中科院分区:
医学4区
文献类型:
--
作者:
Qin Liping;Zeng Jianping;Shi Nannan;Chen Liu;Wang Li

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结直肠癌是世界上最常见的恶性肿瘤之一。虽然对CRC的发病机制进行了研究,但CRC肿瘤发生的分子机制仍不清楚。在本研究中,加权基因共表达网络分析进行基因表达Omnibus(GEO)数据集GSE 87211,以分析参与大肠癌发病机制的关键模块。接下来,对关键模块基因进行基因本体论和京都基因和基因组百科全书富集分析,以分析所涉及的功能途径。使用Cytoscape平台筛选枢纽基因,并通过第二个GEO数据集GSE 21510进行验证。最后,在2个关键模块(绿色和棕色模块)中鉴定出10个枢纽基因,作为与CRC肿瘤发生最显著相关的基因。来自绿色模块的5个枢纽基因包括I型胶原α1链、XII型胶原α1链、含1的胶原三螺旋重复序列、β-胡萝卜素亚基(INHBA)和染色体盒2(CBX 2),而来自棕色模块的5个枢纽基因包括雌激素样蛋白2(BEST 2)、碳酸酐酶2、胰高血糖素、溶质载体家族4成员4和胶质细胞调节素。这2个关键模块与10个hub基因可能通过细胞外基质通路、PI 3 K-Akt和趋化因子信号通路调控CRC的发生和发展,从而为理解CRC复杂的肿瘤发生机制提供参考。值得注意的是,很少有研究报道了CRC的发病机制与3个确定的枢纽基因,INHBA,CBX 2和BEST 2。建议进一步研究这些基因在CRC中的分子机制。
Colorectal cancer (CRC) is one of the most common malignant diseases in the world. Although mechanistic studies have been conducted on the pathogenesis of CRC, the molecular mechanism of CRC tumorigenesis remains unclear. In the present study, the weighted gene co-expression network analysis was performed for the Gene Expression Omnibus (GEO) dataset GSE87211, in order to analyze the key modules involved in the pathogenesis of CRC. Next, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the key module genes to analyze the functional pathways involved. The hub genes were screened using the Cytoscape platform and verified by a second GEO dataset, GSE21510. Finally, 10 hub genes were identified in 2 key modules (the green and brown modules) as the genes most significantly associated with the tumorigenesis of CRC. The 5 hub genes from the green module included collagen type I α1 chain, collagen type XII α1 chain, collagen triple helix repeat containing 1, inhibin subunit βa (INHBA) and chromobox 2 (CBX2), while the 5 hub genes from the brown module included bestrophin 2 (BEST2), carbonic anhydrase 2, glucagon, solute carrier family 4 member 4 and gliomedin. The 2 key modules with the 10 hub genes identified may regulate the occurrence and development of CRC through the extracellular matrix pathway, PI3K-Akt and chemokine signaling pathways, thus providing a reference for understanding the complex mechanism of tumorigenesis in CRC. Of note, few studies have reported the pathogenesis of CRC with the 3 identified hub genes, INHBA, CBX2 and BEST2. Further investigation of the molecular mechanism of these genes in CRC is recommended.
DOI: 10.1002/cam4.1484
发表时间: 2018-06
期刊: Cancer medicine
影响因子: 4
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