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Identification of intestinal flora-related key genes and therapeutic drugs in colorectal cancer
BMC Medical Genomics ( IF 2.7 ) Pub Date : 2020-11-16 , DOI: 10.1186/s12920-020-00810-0
Jiayu Zhang , Huaiyu Zhang , Faping Li , Zheyu Song , Yezhou Li , Tiancheng Zhao

Colorectal cancer (CRC) is a multifactorial tumor and a leading cause of cancer-specific deaths worldwide. Recent research has shown that the alteration of intestinal flora contributes to the development of CRC. However, the molecular mechanism by which intestinal flora influences the pathogenesis of CRC remains unclear. This study aims to explore the key genes underlying the effect of intestinal flora on CRC and therapeutic drugs for CRC. Intestinal flora-related genes were determined using text mining. Based on The Cancer Genome Atlas database, differentially expressed genes (DEGs) between CRC and normal samples were identified with the limma package of the R software. Then, the intersection of the two gene sets was selected for enrichment analyses using the tool Database for Annotation, Visualization and Integrated Discovery. Protein interaction network analysis was performed for identifying the key genes using STRING and Cytoscape. The correlation of the key genes with overall survival of CRC patients was analyzed. Finally, the key genes were queried against the Drug-Gene Interaction database to find drug candidates for treating CRC. 518 genes associated with intestinal flora were determined by text mining. Based on The Cancer Genome Atlas database, we identified 48 DEGs associated with intestinal flora, including 25 up-regulated and 23 down-regulated DEGs in CRC. The enrichment analyses indicated that the selected genes were mainly involved in cell–cell signaling, immune response, cytokine-cytokine receptor interaction, and JAK-STAT signaling pathway. The protein–protein interaction network was constructed with 13 nodes and 35 edges. Moreover, 8 genes in the significant cluster were considered as the key genes and chemokine (C-X-C motif) ligand 8 (CXCL8) correlated positively with the overall survival of CRC patients. Finally, a total of 24 drugs were predicted as possible drugs for CRC treatment using the Drug-Gene Interaction database. These findings of this study may provide new insights into CRC pathogenesis and treatments. The prediction of drug-gene interaction is of great practical significance for exploring new drugs or novel targets for existing drugs.

中文翻译:

大肠癌肠道菌群相关关键基因和治疗药物的鉴定

大肠癌(CRC)是一种多因素肿瘤,是全球范围内因癌症而导致死亡的主要原因。最近的研究表明,肠道菌群的改变有助于CRC的发展。然而,肠菌群影响CRC发病机理的分子机制仍不清楚。这项研究旨在探讨肠道菌群对CRC和CRC治疗药物产生影响的关键基因。使用文本挖掘确定肠道菌群相关基因。根据The Cancer Genome Atlas数据库,使用R软件的limma软件包识别了CRC与正常样品之间的差异表达基因(DEG)。然后,使用“注释,可视化和集成发现”数据库工具选择两个基因集的交集进行富集分析。使用STRING和Cytoscape进行蛋白质相互作用网络分析以鉴定关键基因。分析了关键基因与CRC患者总生存的相关性。最后,针对药物基因相互作用数据库查询关键基因,以找到治疗CRC的候选药物。通过文本挖掘确定了与肠道菌群相关的518个基因。基于癌症基因组图谱数据库,我们鉴定了48个与肠道菌群相关的DEG,包括CRC中25个上调的DEG和23个下调的DEG。富集分析表明,所选基因主要参与细胞间信号转导,免疫应答,细胞因子-细胞因子受体相互作用和JAK-STAT信号通路。蛋白质-蛋白质相互作用网络由13个节点和35个边缘组成。此外,重要基因簇中的8个基因被认为是关键基因,趋化因子(CXC基序)配体8(CXCL8)与CRC患者的总体生存呈正相关。最后,使用Drug-Gene Interaction数据库预测了总共24种药物可能是用于CRC治疗的药物。这项研究的这些发现可能为CRC发病机理和治疗提供新的见解。药物基因相互作用的预测对于探索新药或现有药物的新靶标具有重要的现实意义。这项研究的这些发现可能为CRC发病机理和治疗提供新的见解。药物基因相互作用的预测对于探索新药或现有药物的新靶标具有重要的现实意义。这项研究的这些发现可能为CRC发病机理和治疗提供新的见解。药物基因相互作用的预测对于探索新药或现有药物的新靶标具有重要的现实意义。
更新日期:2020-11-16
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