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通过生物信息学分析鉴定与结直肠癌相关的关键基因和通路。

Identification of crucial genes and pathways associated with colorectal cancer by bioinformatics analysis.

作者信息

Liu Xiaoqun, Liu Xiangdong, Qiao Tiankui, Chen Wei

机构信息

Center for Tumor Diagnosis and Therapy, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China.

Department of Ophthalmology, Jinshan Hospital, Fudan University, Shanghai 201508, P.R. China.

出版信息

Oncol Lett. 2020 Mar;19(3):1881-1889. doi: 10.3892/ol.2020.11278. Epub 2020 Jan 9.

Abstract

Colorectal cancer (CRC) is a prevalent malignant tumour type arising from the colon and rectum. The present study aimed to explore the molecular mechanisms of the development and progression of CRC. Initially, differentially expressed genes (DEGs) between CRC tissues and corresponding non-cancerous tissues were obtained by analysing the GSE15781 microarray dataset. The Database for Annotation, Visualization and Integrated Discovery was then utilized for functional and pathway enrichment analysis of the DEGs. Subsequently, a protein-protein interaction (PPI) network was created using the Search Tool for the Retrieval of Interacting Genes and Proteins database and visualized by Cytoscape software. Furthermore, CytoNCA, a Cytoscape plugin, was used for centrality analysis of the PPI network to identify crucial genes. Finally, UALCAN was employed to validate the expression of the crucial genes and to estimate their effect on the survival of patients with colon cancer by Kaplan-Meier curves and log-rank tests. A total of 1,085 DEGs, including 496 upregulated and 589 downregulated genes, were screened out. The DEGs identified were enriched in various pathways, including 'metabolic pathway', 'cell cycle', 'DNA replication', 'nitrogen metabolism', 'p53 signalling' and 'fatty acid degradation'. PPI network analysis suggested that interleukin-6, MYC, NOTCH1, inhibin subunit βA (INHBA), CDK1, cyclin (CCN)B1 and CCNA2 were crucial genes, and their expression levels were markedly upregulated. Survival analysis suggested that upregulated INHBA significantly decreased the survival probability of patients with CRC. Conversely, upregulation of CCNB1 and CCNA2 expression levels were associated with increased survival probabalities. The identified DEGs, particularly the crucial genes, may enhance the current understanding of the genesis and progression of CRC, and certain genes, including INHBA, CCNB1 and CCNA2, may be candidate diagnostic and prognostic markers, as well as targets for the treatment of CRC.

摘要

结直肠癌(CRC)是一种起源于结肠和直肠的常见恶性肿瘤类型。本研究旨在探讨CRC发生发展的分子机制。首先,通过分析GSE15781芯片数据集获得CRC组织与相应癌旁组织之间的差异表达基因(DEGs)。然后利用注释、可视化和整合发现数据库对DEGs进行功能和通路富集分析。随后,使用检索相互作用基因和蛋白质的搜索工具数据库创建蛋白质-蛋白质相互作用(PPI)网络,并通过Cytoscape软件进行可视化。此外,使用Cytoscape插件CytoNCA对PPI网络进行中心性分析以识别关键基因。最后,利用UALCAN验证关键基因的表达,并通过Kaplan-Meier曲线和对数秩检验评估其对结肠癌患者生存的影响。共筛选出1085个DEGs,其中包括496个上调基因和589个下调基因。所鉴定的DEGs富集于多种通路,包括“代谢途径”、“细胞周期”、“DNA复制”、“氮代谢”、“p53信号通路”和“脂肪酸降解”。PPI网络分析表明,白细胞介素-6、MYC、NOTCH1、抑制素亚基βA(INHBA)、细胞周期蛋白依赖性激酶1(CDK1)、细胞周期蛋白(CCN)B1和CCNA2是关键基因,且它们的表达水平显著上调。生存分析表明,INHBA上调显著降低了CRC患者的生存概率。相反,CCNB1和CCNA2表达水平上调与生存概率增加相关。所鉴定的DEGs,特别是关键基因,可能会加深目前对CRC发生发展的理解,某些基因,包括INHBA、CCNB1和CCNA2,可能是候选的诊断和预后标志物,以及CRC治疗的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1acb/7039150/eb7918d4a8a1/ol-19-03-1881-g00.jpg

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