>
网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
基于生物信息学分析NEIL3在肝细胞癌中的表达及其临床意义
作者:张建国1  何亮1  王久阳2  姜涛1 
单位:1. 北京市平谷区医院 普外科, 北京 101200;
2. 北京市平谷区医院 病理科, 北京 101200
关键词:肝细胞癌 Nei核酸内切酶Ⅷ样3 生物信息学 
分类号:R735.7
出版年·卷·期(页码):2022·41·第三期(386-393)
摘要:

目的:基于生物信息学分析Nei核酸内切酶Ⅷ样3(Nei endonuclease Ⅷ-like 3,NEIL3)在肝细胞癌(hepatocellular carcinoma,HCC)中的表达和临床意义。方法:利用TCGA数据库的mRNA数据和临床数据分析NEIL3在肝细胞癌中的表达和临床意义。使用GEPIA和Kaplan-Meier数据库分析NEIL3表达对HCC患者预后的影响。使用UALCAN和cBioPortal数据库分析NEIL3在HCC中的甲基化水平。使用STRING、Metascape和LinkedOmics探索NEIL3在HCC中的潜在作用机制。结果:与正常组相比,NEIL3在HCC显著高表达。临床相关性分析结果显示,NEIL3表达与患者的病理分期及肿瘤大小呈负相关。Kaplan-Meier生存曲线显示,NEIL3高表达与HCC患者较差的总体生存期、无病生存期、无进展生存期、无复发生存期有关。表观遗传学研究发现,NEIL3基因的低甲基化可能是NEIL3在HCC中表达上调的原因之一。功能富集分析发现,NEIL3可能通过参与细胞周期、DNA复制、同源重组、错配修复、p53信号通路、碱基切除修复、剪接体和乙型肝炎相关等信号通路促进HCC发生发展。结论:生物信息学分析显示,NEIL3在HCC组织中显著高表达,且与患者的不良临床结局相关,可作为HCC的潜在治疗靶点和预后生物标志物。

Objective: To analyze the expression and clinical significance of Nei endonuclease Ⅷ-like 3(NEIL3) in hepatocellular carcinoma(HCC) based on bioinformatics. Methods: The expression and clinical significance of NEIL3 in HCC were analyzed using mRNA data from the TCGA database and clinical data. The impact of NEIL3 expression on the prognosis of HCC patients was analyzed using the GEPIA and Kaplan-Meier databases. Analysis of NEIL3 methylation levels in HCC was performed using the UALCAN and cBioPortal databases. The potential mechanisms of NEIL3 action in HCC were explored using STRING, Metascape and LinkedOmics. Results: NEIL3 was significantly overexpressed in HCC compared to the normal group. Kaplan-Meier survival curves showed that high NEIL3 expression was associated with poor overall survival, disease-free survival, progression-free survival and recurrence-free survival in HCC patients. Epigenetic studies revealed that hypomethylation of the NEIL3 gene may contribute to the upregulation of NEIL3 expression in HCC. Finally, functional enrichment analysis revealed that NEIL3 may contribute to HCC development by participating in signaling pathways such as cell cycle, DNA replication, homologous recombination, mismatch repair, p53 signaling pathway, base excision repair, spliceosome and hepatitis B. Conclusion: Bioinformatics analysis has showed that NEIL3 is significantly highly expressed in HCC tissues and correlated with poor clinical outcome in patients, and may serve as a potential prognostic biomarker and therapeutic target for HCC.

参考文献:

[1] GRAVITZ L.Liver cancer[J].Nature,2014,516(7529):S1.
[2] VILLANUEVA A.Hepatocellular carcinoma[J].New Engl J Med,2019,380(15):1450-1462.
[3] HARTKE J,JOHNSON M,GHABRIL M.The diagnosis and treatment of hepatocellular carcinoma[J].Semin Diang Pathol,2017,34(2):153-159.
[4] FLEMING A M,ZHU J,HOWPAY MANAGE S A,et al.Human NEIL3 gene expression regulated by epigenetic-like oxidative DNA modification[J].J Am Chem Soc,2019,141(28):11036-11049.
[5] ZHAO C,LIU J,ZHOU H,et al.NEIL3 may act as a potential prognostic biomarker for lung adenocarcinoma[J].Cancer Cell Int,2021,21(1):228.
[6] HILDRESTRAND G A,NEURAUTER C G,DIEP D B,et al.Expression patterns of Neil3 during embryonic brain development and neoplasia[J].BMC Neurosci,2009,10(5):45.
[7] WANG Y,XU L,SHI S,et al.Deficiency of NEIL3 enhances the chemotherapy resistance of prostate cancer[J].Int J Mol Sci,2021,22(8):4098.
[8] TOMCZAK K,CZERWINSKA P,WIZNEROWICZ M.The cancer genome atlas(TCGA):an immeasurable source of knowledge[J].Contemp Oncol(Pozn),2015,19(1A):A68-77.
[9] TANG Z,LI C,KANG B,et al.GEPIA:a web server for cancer and normal gene expression profiling and interactive analyses[J].Nucleic Acids Res,2017,45(W1):W98-W102.
[10] NAGY Á,MUNK CSY G,GYRFFY B.Pancancer survival analysis of cancer hallmark genes[J].Sci Rep,2021,11(1):6047.
[11] CHANDRASHEKAR D S,BASHEL B,BALASUBRAMANYA S A H,et al.UALCAN:a portal for facilitating tumor subgroup gene expression and survival analyses[J].Neoplasia,2017,19(8):649-658.
[12] CERAMI E,GAO J,DOGRUSOZ U,et al.The cBio cancer genomics portal:an open platform for exploring multidimensional cancer genomics data[J].Cancer Discov,2012,2(5):401-404.
[13] SZKLARCZYK D,FRANCESCHINI A,WYDER S,et al.STRING v10:protein-protein interaction networks,integrated over the tree of life[J].Nucleic Acids Res,2015,43(Database issue):D447-D452.
[14] ZHOU Y,ZHOU B,PACHE L,et al.Metascape provides a biologist-oriented resource for the analysis of systems-level datasets[J].Nat Commun,2019,10(1):1523.
[15] VASAIKAR S V,STRAUB P,WANG J,et al.LinkedOmics:analyzing multi-omics data within and across 32 cancer types[J].Nucleic Acids Res,2018,46(D1):D956-D963.
[16] FORNER A,REIG M,BRUIX J.Hepatocellular carcinoma[J].Lancet,2018,391(10127):1301-1314.
[17] EVAN G I,VOUSDEN K H.Proliferation,cell cycle and apoptosis in cancer[J].Nature,2001,411(6835):342-348.
[18] KITAO H,IIMORI M,KATAOKA Y,et al.DNA replication stress and cancer chemotherapy[J].Cancer Sci,2018,109(2):264-271.
[19] PRAKASH R,ZHANG Y,FENG W,et al.Homologous recombination and human health:the roles of BRCA1,BRCA2,and associated proteins[J].CSH Perspect Biol,2015,7(4):a016600.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 413795 位访问者


copyright ©《东南大学学报(医学版)》编辑部
联系电话:025-83272481 83272483
电子邮件:
bjb@pub.seu.edu.cn

苏ICP备09058364