基于生信分析筛选鼻咽癌放疗抵抗干性相关基因及相关通路的研究  

Identification of genes and pathways related to radioresistance associated tumor stemness in nasopharyngeal carcinoma based on bioinformatics analysis

作　　者：陈劲海 徐亚丽[1] Chen Jinhai;Xu Yali(Department of Otolaryngology,Second Affiliated Hospital of Guangzhou Medical University,Guangzhou 510260,China)

机构地区：[1]广州医科大学附属第二医院耳鼻喉科,广东广州510260

出　　处：《广州医科大学学报》2022年第3期32-37,共6页Academic Journal of Guangzhou Medical University

基　　金：广东省医学科学技术研究基金(A2022351)。

摘　　要：目的:基于生物信息学分析探讨鼻咽癌放疗抵抗干性相关基因及信号通路。方法:从GEO数据库下载鼻咽癌数据集GSE32389,并重新分析相关原始数据。构建肿瘤干性评分机器学习模型和放疗抵抗统计模型,识别鼻咽癌干性放疗抵抗相关基因;同时进行基因GO和KEGG功能富集分析,寻找影响肿瘤放疗效果的重要细胞分子过程及相关通路;通过结合肿瘤相关转录因子、肿瘤放疗抵抗干性相关基因和富集的肿瘤特征通路构建网络,甄别放疗抵抗网络上起重要作用的核心基因。结果:识别放疗抵抗干性相关差异表达相关基因,共筛选到27个,分别为ACTC1,AGTRAP,CHRM5,CNIH3,DPT,FAM8A1,FANCL,HAS2,HOXB2,IGLC1,IL1RN,KIFAP3,LNX1,MRPL13,MYL6,NLRP14,PRKDC,RABAC1,RABGAP1L,RALA,SENP5,SERPING1,SMDT1,SPAG7,TMA16,TMTC4和ZBTB33。这些基因主要参与了B细胞介导免疫、免疫效应过程和分子介导的免疫反应等生物过程;并富集于JAK-STAT、Cytokine-cytokine receptor interaction等信号通路。通过网络结构分析,识别放疗抵抗重要的功能模块,同时根据网络结点的连接度,甄别出PRKDC、HOXB2和ZBTB33在网络中有着重要的作用,可作为鼻咽癌放疗增敏的侯选标靶。结论:本研究通过生物信息学方法识别鼻咽癌放疗抵抗干性相关基因和治疗作用靶点,用以增敏鼻咽癌放疗效果,对于改善和提高患者生存质量及预后至关重要,其具有重要的临床意义。Objective:To identify the genes and pathways related to radioresistance associated tumor stemness in nasopharyngeal carcinoma(NPC)based on bioinformatics analysis.Methods:The nasopharyngeal carcinoma dataset GSE32389 was downloaded from the GEO database for re-analysis of the relevant raw data.Machine-learning algorithm for tumor stemness scoring and statistical module were constructed to identify the genes potentiall related to radioresistance associated tumor stemness in NPC.GO and KEGG function enrichment analyses were performed to explore the major intracellular molecular processes and related pathways that may affect the outcome of tumor radiotherapy.A co-expression network in NPC was generated to incorporate the tumor-associated transcription factors,genes related to radioresistance associated tumor stemness,and enriched pathways of tumor signatures,to determine the hub genes that are playing an important role in this network.Results:A total of 27 differentially expressed genes related to stemness of radiotherapy resistance were identified,including ACTC1,AGTRAP,CHRM5,CNIH3,DPT,FAM8A1,FANCL,HAS2,HOXB2,IGLC1,IL1RN,KIFAP3,LNX1,MRPL13,MYL6,NLRP14,PRKDC,RABAC1,RABGAP1L,RALA,SENP5,SERPING1,SMDT1,SPAG7,TMA16,TMTC4 and ZBTB33.These genes are mainly involved in GO biological processes such as B cell-mediated immunity,immune effector process and molecular-mediated immune response,and are enriched in the JAK-STAT,and cytokine-cytokine receptor interaction signaling pathways.According to network structural analysis for identification of major functional modules of radiotherapy resistance,and the connectance of network nodes,PRKDC,HOXB2 and ZBTB33 were determined to have an important role in this network and can be used as candidate targets for radiosensitization in nasopharyngeal carcinoma.Conclusion:In this bioinformatics study,several genes and therapeutic targets related to radioresistance associated tumor stemness in NPC are identified,and can be used for radiosensitization in NPC patients.These findings are clini

关 键 词：鼻咽部肿瘤 肿瘤干细胞 放疗抵抗 

分 类 号：R739.6[医药卫生—肿瘤]