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结直肠癌奥沙利铂耐药关键基因的生物信息学分析及意义
引用本文:徐建波,周星宇,谢琴琴,欧信德,叶锦宁,彭建军,吴晖. 结直肠癌奥沙利铂耐药关键基因的生物信息学分析及意义[J]. 中华普通外科学文献(电子版), 2020, 14(5): 349-354. DOI: 10.3877/cma.j.issn.1674-0793.2020.05.007
作者姓名:徐建波  周星宇  谢琴琴  欧信德  叶锦宁  彭建军  吴晖
作者单位:1. 510080 广州,中山大学附属第一医院胃肠外科中心2. 510080 广州,中山大学护理学院
基金项目:国家自然科学基金资助项目(81672343,81871915); 广东省自然科学基金资助项目(2015A030313053,2017A030313570); 广州市科学技术计划项目(201607010050)
摘    要:目的筛选与结直肠癌(CRC)中奥沙利铂(OXA)耐药性相关的基因和通路。 方法首先通过GEO数据库分析GSE76092的基因表达谱,筛选出CRC的OXA敏感和OXA耐药细胞系之间的差异表达基因(DEGs)。利用DAVID数据库进行基因本体论(Go)分析和京都基因和基因组百科全书(KEGG)通路分析。通过STRING工具构建蛋白质-蛋白质相互作用(PPI)网络。经MCODE插件选择关键基因,并利用GEPIA工具进行生存分析。最后使用miRWalk数据库预测相关的miRNA。 结果通过数据分析总共获得474个DEGs,并筛选了相关的信号通路和PPI网络。筛选出15个中心基因,其中7个显著参与NF-κB和趋化因子信号等通路。对7个关键基因的生存分析表明,CXCL8、IL-1β和PTGS2表达水平与CRC患者的总体生存相关。预测hsa-miR-6893-5p、hsa-miR-7851-3p和hsa-miR-96-3p是OXA耐药相关核心miRNA。 结论基于生物信息学筛选出来的OXA耐药关键基因和信号通路,为CRC中OXA耐药的潜在机制提供更深入的了解。

关 键 词:结直肠肿瘤  奥沙利铂  耐药性  生物信息学分析  
收稿时间:2020-06-05

Bioinformatics analysis and significance of key genes for oxaliplatin resistance in colorectal cancer
Jianbo Xu,Xingyu Zhou,Qinqin Xie,Xinde Ou,Jinning Ye,Jianjun Peng,Hui Wu. Bioinformatics analysis and significance of key genes for oxaliplatin resistance in colorectal cancer[J]. Chinese Journal of General Surgery(Electronic Version), 2020, 14(5): 349-354. DOI: 10.3877/cma.j.issn.1674-0793.2020.05.007
Authors:Jianbo Xu  Xingyu Zhou  Qinqin Xie  Xinde Ou  Jinning Ye  Jianjun Peng  Hui Wu
Affiliation:1. Department of Gastrointestinal Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China2. School of Nursing, Sun Yat-sen University, Guangzhou 510080, China
Abstract:ObjectiveTo identify the gene signatures and pathways associated with oxaliplatin (OXA) resistance in colorectal cancer (CRC). MethodsThe gene expression profile of GSE76092 was analyzed from the Gene Expression Omnibus (GEO) database. Via GEO2R tool, differentially expressed genes (DEGs) between OXA-sensitive and OXA-resistant cell lines of CRC were sorted. Then the DAVID online tool was used to analyze Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway. Next, protein-protein interaction (PPI) networks were constructed by STRING and modified by Cytoscape. The hub genes were selected via MCODE plugin and the survival analysis was performed on the GEPIA. Finally, the miRWalk was used to predict the gene-related miRNAs. ResultsA total of 474 DEGs were obtained. The DEGs-related GO and KEGG pathways were identified and the PPI networks were built. Among them, 15 hub genes were screened out, 7 of which were significantly involved in NF-kappa B signaling pathway and Chemokine signaling pathway. The survival analysis of the 7 key genes indicated that CXCL8, IL-1β and PTGS2 expression levels were associated with overall survival. Finally, hsa-miR-6893-5p, hsa-miR-7851-3p and hsa-miR-96-3p were predicted as the core miRNAs. ConclusionOn the basis of bioinformatical methods, key genes and pathways in OXA-resistant CRC were identified, which could provide a deeper understanding of underlying mechanisms of OXA resistance in CRC.
Keywords:Colorectal Neoplasms  Oxaliplatin  Resistance  Bioinformatics analysis  
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