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Identification of novel biomarkers and small molecule drugs in human colorectal cancer by microarray and bioinformatics analysis

机译:微阵列与生物信息学分析鉴定人结肠直肠癌的新型生物标志物和小分子药物

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摘要

Abstract Background Colorectal cancer (CRC) is one of the most common malignant tumors. In the present study, the expression profile of human multistage colorectal mucosa tissues, including healthy, adenoma, and adenocarcinoma samples was downloaded to identify critical genes and potential drugs in CRC. Methods Expression profiles, GSE33113 and GSE44076, were integrated using bioinformatics methods. Differentially expressed genes (DEGs) were analyzed by R language. Functional enrichment analyses of the DEGs were performed using the Database for Annotation, visualization, and integrated discovery (DAVID) database. Then, the search tool for the retrieval of interacting genes (STRING) database and Cytoscape were used to construct a protein–protein interaction (PPI) network and identify hub genes. Subsequently, survival analysis was performed among the key genes using Gene Expression Profiling Interactive Analysis (GEPIA). Connectivity Map (CMap) was used to query potential drugs for CRC. Results A total of 428 upregulated genes and 751 downregulated genes in CRC were identified. The functional changes of these DEGs were mainly associated with cell cycle, oocyte meiosis, DNA replication, p53 signaling pathway, and progesterone‐mediated oocyte maturation. A PPI network was identified by STRING with 482 nodes and 2,368 edges. Survival analysis revealed that high mRNA expression of AURKA, CCNB1, CCNF, and EXO1 was significantly associated with longer overall survival. Moreover, CMap predicted a panel of small molecules as possible adjuvant drugs to treat CRC. Conclusion Our study found key dysregulated genes involved in CRC and potential drugs to combat it, which may provide novel insights and potential biomarkers for prognosis, as well as providing new CRC treatments.
机译:抽象背景结肠直肠癌(CRC)是最常见的恶性肿瘤之一。在本研究中,人类多段结直肠黏膜组织,包括健康,腺瘤,腺癌和样品的表达谱下载,以确定在CRC的关键基因和潜在药物。方法表达谱,GSE33113和GSE44076,采用生物信息学方法结合起来。差异表达的基因(DEGS)分别用R语言分析。使用注释,可视化数据库进行了DEGS的功能富集分析,并集成发现(DAVID)数据库。然后,对于相互作用基因(STRING)数据库和Cytoscape的的检索搜索工具用于构建一个蛋白质 - 蛋白质相互作用(PPI)网络,并确定集线器基因。随后,使用基因表达谱交互式分析(GEPIA)的关键基因中进行生存分析。联系图(CMap的)来查询潜在的药物CRC。结果共428个上调基因和CRC 751组下调的基因进行了鉴定。这些DEGS的功能的改变主要与细胞周期,卵母细胞减数分裂,DNA复制,p53信号传导途径,和孕激素介导的卵母细胞成熟相关联。甲PPI网络的鉴定通过用482级的节点和2368层的边缘STRING。生存分析显示AURKA,CCNB1,CCNF的高表达,并EXO1是显著较长的总生存期相关。此外,预测CMap的小分子尽可能佐剂药物来治疗CRC的一个面板。结论:我们的研究发现,参与CRC和潜在的药物来对付它的关键基因失调,这可能预后提供新的见解和潜在生物标志物,以及提供新的CRC的治疗。

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