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Identification of key regulators associated with colon cancer prognosis and pathogenesis
Journal of Cell Communication and Signaling ( IF 4.1 ) Pub Date : 2021-03-26 , DOI: 10.1007/s12079-021-00612-8
Narges Toolabi 1 , Fattane Sam Daliri 1 , Amir Mokhlesi 1 , Mahmood Talkhabi 1
Affiliation  

Colon cancer (CC) is the fourth deadliest cancer in the world. New insights into prognostication might be helpful to define the optimal adjuvant treatments for patients in routine clinical practice. Here, a microarray dataset with 30 primary tumors and 30 normal samples was analyzed using GEO2R to find differentially expressed genes (DEGs). Then, DAVID, KEGG, ChEA and X2K were used to analyze DEGs-related Gene Ontology, pathways, transcription factors (TFs) and kinases, respectively. Protein–protein interaction (PPI) networks were constructed using the STRING database and Cytoscape. The modules and hub genes of DEGs was determined through MCODE and CytoHubba plugins, and the expression of hub genes was verified using GEPIA. To find microRNAs and metabolites associated with DEGs, miRTarBase and HMDB were used, respectively. It was found that 233 and 373 genes were upregulated and downregulated in CC, respectively. GO analysis showed that the upregulated DEGs were mainly involved in mitotic nuclear division and cell division. Top 10 hub genes were identified, including AURKB, CDK1, DLGAP5, AURKA, CCNB2, CCNB1, BUB1B, CCNA2, KIF20A and BUB1. Whereas, FOMX1, E2F7, E2F1, E2F4 and AR were identified as top 5 TFs in CC. Moreover, CDK1, CDC2, MAPK14, ATM and CK2ALPHA was identified as top 5 kinases in CC. miRNAs analysis showed that Hsa-miR-215-5p hsa-miR-193b-3p, hsa-miR-192-5p and hsa-miR-16-5p could target the largest number of CC genes. Taken together, CC-related genes, especially the hub genes, TFs, and metabolites might be used as novel biomarkers for CC, as well as for diagnosis and guiding therapeutic strategies for CC.



中文翻译:

鉴定与结肠癌预后和发病机制相关的关键调节因子

结肠癌(CC)是世界上第四大致命癌症。对预后的新见解可能有助于在常规临床实践中为患者确定最佳辅助治疗。在这里,使用 GEO2R 分析了包含 30 个原发性肿瘤和 30 个正常样本的微阵列数据集,以查找差异表达基因 (DEG)。然后,使用DAVID、KEGG、ChEA和X2K分别分析DEGs相关的基因本体、通路、转录因子(TF)和激酶。使用 STRING 数据库和 Cytoscape 构建蛋白质-蛋白质相互作用 (PPI) 网络。通过MCODE和CytoHubba插件确定DEG的模块和hub基因,并使用GEPIA验证hub基因的表达。为了寻找与 DEG 相关的 microRNA 和代谢物,分别使用了 miRTarBase 和 HMDB。结果发现,CC 中分别有 233 个和 373 个基因上调和下调。GO分析显示上调的DEGs主要参与有丝分裂核分裂和细胞分裂。确定了前 10 个枢纽基因,包括 AURKB、CDK1、DLGAP5、AURKA、CCNB2、CCNB1、BUB1B、CCNA2、KIF20A 和 BUB1。而 FOMX1、E2F7、E2F1、E2F4 和 AR 被确定为 CC 中排名前 5 的 TF。此外,CDK1、CDC2、MAPK14、ATM 和 CK2ALPHA 被确定为 CC 中排名前 5 的激酶。miRNA分析显示,hsa-miR-215-5p、hsa-miR-193b-3p、hsa-miR-192-5p和hsa-miR-16-5p可以靶向最大数量的CC基因。综上所述,CC相关基因,特别是中心基因、转录因子和代谢物可能被用作CC的新型生物标志物,以及用于CC的诊断和指导治疗策略。

更新日期:2021-03-26
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