多个GEO芯片联合分析筛选鼻咽癌易感基因

doi:10.3969/j.issn.2095-9400.2020.01.001

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (2031 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的：筛选鼻咽癌的关键基因，探讨鼻咽癌发病机制。方法：从公共基因芯片数据库（GEO）搜索有关鼻咽癌表达的数据，联合R语言分析鼻咽癌组织与正常鼻咽组织差异表达的基因；利用基因本体（GO）数据库和京都基因与基因组百科全书（KEGG）通路数据库对差异表达的基因进行富集和功能注释。基于STRING数据库及Cytoscape软件构建蛋白质相互作用网络，分析其关键基因簇及网络节点。结果：共纳入3套鼻咽癌基因芯片数据，选出在≥3个数据集中有交集的差异表达基因116个，其中上调基因69个，下调基因47个。差异表达基因GO富集分析发现细胞分裂异常、蛋白结合改变，纺锤体装配异常、细胞外泌体功能改变与鼻咽癌发生发展相关；鼻咽癌组织细胞内部分信号通路发生显著改变，包括DNA修复、细胞外基质受体相互作用、细胞周期、小细胞肺癌、人T细胞白血病病毒1感染等。蛋白质相互作用网络提示存在3个重要的基因簇及4个关键基因。结论：利用生物信息学方法能有效筛选目标基因和信号通路，为鼻咽癌的治疗提供新的策略。

	服务
	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	王晓琼
	金巧智
	陈武兵
	蔡志毅

关键词 ：鼻咽癌, 生物信息学, 信号通路

Abstract：Objective: To screen the key genes of nasopharyngeal carcinoma (NPC) and to explore the pathogenesis of nasopharyngeal carcinoma. Methods: The differentially expressed genes (DEGs) in NPC were identified by Gene Expression Omnibus (GEO) combined with R language. Gene ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for enrichment and functional annotation of DEGs. A protein-protein interaction (PPI) network was constructed based on STRING database and the key gene clusters and network nodes of NPC were further analyzed by Cytoscape software. Results: A total of 3 sets of nasopharyngeal cancer gene chip data were included. 116 differentially expressed genes with intersection in this 3 data sets were selected, including 69 up-regulated genes and 47 down-regulated genes. GO enrichment analysis of differentially expressed genes revealed abnormal cell division and spindle assembly, changes in protein biding and in extracellular body function, which were associated with the occurrence and development of nasopharyngeal carcinoma. Some intracellular signaling pathways of nasopharyngeal carcinoma were significantly altered, including DNA repair, extracellular matrix receptor interaction, cell cycle small cell lung cancer, human T-cell leukemia virus 1 infection, etc. The protein interaction network suggests that there are three important gene clusters and four key genes. Conclusion: Bioinformatics can effectively screen target genes and signal pathways, which provides new ideas for the treatment of nasopharyngeal carcinoma.

Key words： nasopharyngeal carcinoma bioinformatics signaling pathway

收稿日期: 2019-04-04

基金资助:国家自然科学基金青年基金资助项目（81500804）；浙江省医药卫生科技计划项目（2019RC311）。

通讯作者: 蔡志毅，主任医师，Email：caizhiyi1962@163.com。

作者简介: 王晓琼（1992-），女，浙江温州人，硕士生。

链接本文:

https://xb.wmu.edu.cn/CN/10.3969/j.issn.2095-9400.2020.01.001 或 https://xb.wmu.edu.cn/CN/Y2020/V50/I1/1

[1] TORRE L A, BRAY F, SIEGEL R L, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108.
[2] WU F, WANG R, LU H, et al. Concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: treatment outcomes of a prospective, multicentric clinical study[J]. Radiother Oncol, 2014, 112(1): 106-111.
[3] CHUA M L K, WEE J T S, HUI E P, et al. Nasopharyngeal carcinoma[J]. Lancet, 2016, 387(10022): 1012-1024.
[4] HUANG DA W, SHERMAN B T, LEMPICKI R A. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists[J]. Nucleic Acids Res, 2009, 37(1): 1-13
[5] 陈林波, 李先鹏, 姜昊, 等. 肝癌相关基因的生物信息学分析及功能预测[J]. 温州医科大学学报, 2018, 48(11): 828-832.
[6] SENGUPTA S, DEN BOON J A, CHEN I H, et al. Genome-wide expression profiling reveals EBV-associated inhibition of MHC class I expression in nasopharyngeal carcinoma[J]. Cancer 2006, 66(16): 7999-8006.
[7] BOSE S, YAP L F, FUNG M, et al. The ATM tumour suppressor gene is down-regulated in EBV-associated nasopharyngeal carcinoma[J]. J Pathol, 2009, 217(3): 345-52.
[8] BO H, GONG Z, ZHANG W, et al. Upregulated long non-coding RNA AFAP1-AS1 expression is associated with progression and poor prognosis of nasopharyngeal carcinoma [J]. Oncotarget, 2015, 6(24): 20404-20418.
[9] DENG M, ZHANG W, TANG H, et al. Lactotransferrin acts as a tumor suppressor in nasopharyngeal carcinoma by repressing AKT through multiple mechanisms[J]. Oncogene, 2013, 32(36): 4273-4283.
[10] ZHOU Y, ZENG Z, ZHANG W, et al. Lactotransferrin: A candidate tumor suppressor-Deficient expression in human nasopharyngeal carcinoma and inhibition of NPC cell proliferation by modulating the mitogen-activated protein kinase pathway[J]. Int J Cancer, 2008, 123(9): 2065-2072.
[11] SOO R A, WU J, AGGARWAL A, et al. Celecoxib reduces microvessel density in patients treated with nasopharyngeal carcinoma and induces changes in gene expression[J]. Ann Oncol, 2006, 17(11): 1625-1630.
[12] ZHOU Y, XIA L, LIN J, et al. Exosomes in nasopharyngeal carcinoma[J]. J Cancer, 2018, 9(5): 767-777.
[13] KEERTHIKUMAR S, GANGODA L, GHO Y S, et al. Bioinformatics tools for extracellular vesicles research[J]. Methods Mol Biol, 2017, 1545: 189-196.
[14] DE MARCH M, DE BIASIO A. The dark side of the ring: role of the DNA sliding surface of PCNA[J]. Crit Rev Biochem Mol Biol, 2017, 52(6): 663-673.
[15] 莫浩元, 张昌卿, 冯凯涛, 等. 鼻咽癌组织中P53和PCNA表达与临床分期、VCA/IgA、EA/IgA、放射敏感性和预后的关系[J]. 癌症, 2004, 23(115): 1551-1554.
[16] DAS S P, RHIND N. How and why multiple MCMs are loaded at origins of DNA replication[J]. Bioessays, 2016, 38(7): 613-617.
[17] 潘素明, 杜日昌, 彭淑平, 等. 微小染色体维持蛋白2在鼻咽癌中的免疫组织化学表达及临床意义[J]. 中国组织化学与细胞化学杂志, 2016, 25(2): 148-152.
[18] MIYAZAKI T, ARAI S. Two distinct controls of mitotic Cdk1/Cyclin B1 activity requisite for cell growth prior to cell division[J]. Cell Cycle, 2007, 6(12): 1419-1425.
[19] SHIOMI Y, NISHITANI H. Control of genome integrity by RFC complexes; conductors of PCNA loading onto and unloading from chromatin during DNA replication[J]. Genes (Basel), 2017, 8(2): E52.
[20] XIANG J, FANG L, LUO Y, et al. Levels of human replication factor C4, a clamp loader, correlate with tumor progression and predict the prognosis for colorectal cancer[J]. J Transl Med, 2014, 12: 320.
[21] ARAI M, KONDOH N, IMAZEKI N, et al. The knockdown of endogenous replication factor C4 decreases the growth and enhances the chemosensitivity of hepatocellular carcinoma cells[J]. Liver Int, 2009, 29(1): 55-62.