核糖核苷酸还原酶M2在宫颈癌中的表达及机制研究  

Expression and Mechanism of Ribonucleotide Reductase M2 in Cervical Cancer

作　　者：王婷婷 王玉芳 黄楠 WANG Tingting;WANG Yufang;HUANG Nan(Quanzhou Medical College,Quanzhou 362011,China)

机构地区：[1]泉州医学高等专科学校,福建泉州362011

出　　处：《生物化工》2025年第1期19-26,32,共9页Biological Chemical Engineering

基　　金：泉州医学高等专科学校校级重点科技课题(XJK2405A)。

摘　　要：目的:探讨核糖核苷酸还原酶M2(RRM2)在宫颈癌中的表达情况及其与宫颈癌发生发展的潜在分子机制,揭示RRM2作为宫颈癌诊断和预后生物标志物的可能性。方法:从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)下载宫颈癌及其正常对照的mRNA表达数据;分析RRM2在宫颈癌与正常组织中的表达差异;评估RRM2表达对宫颈癌患者总生存期(OS)的预后价值;提取与RRM2显著正/负相关的基因,并构建蛋白相互作用网络;对共表达基因进行基因本体(GO)和京都基因与基因组百科全书(KEGG)信号通路富集分析。采用基因集变异分析(GSVA)方法分析RRM2表达与细胞周期功能的相关性。结果:RRM2在宫颈癌组织中的表达显著高于正常组织(p<0.05)。RRM2高表达的宫颈癌患者OS显著较差(HR:1.700;p=0.031)。共表达分析确定了与RRM2显著正/负相关的前1000个基因,其中TCF19、CDCA8和CENPO为前3个正相关基因,PCMTD1、TP53INP1和ZNF582为前3个负相关基因。GO分析显示,这些基因主要富集于生物调节、代谢过程和刺激反应等生物过程;KEGG分析表明,细胞周期、DNA复制和剪接体是显著富集的信号通路。RRM2表达与宫颈癌细胞周期功能呈正相关,提示RRM2可能通过调节细胞周期促进宫颈癌进展。结论:RRM2在宫颈癌中表达上调并促进宫颈癌进展,可能通过促进肿瘤细胞周期来发挥作用,有望成为宫颈癌诊断和预后的新型生物标志物。Objective:To investigate the expression of ribonucleotide reductase M2(RRM2)in cervical cancer and its potential molecular mechanism with the occurrence and development of cervical cancer,and to reveal the possibility of RRM2 as a biomarker for the diagnosis and prognosis of cervical cancer.Methods:The mRNA expression data of cervical cancer and its normal controls were downloaded from the cancer genome atlas(TCGA)and the gene expression integrated database(GEO).analyze the difference in the expression of RRM2 in cervical cancer and normal tissues.Evaluate the prognostic value of RRM2 expression on overall survival(OS)of cervical cancer patients;the genes significantly positive/negatively correlated with RRM2 are extracted,and the protein interaction network is constructed.Co-expressed genes are analyzed by gene ontology(GO)and kyoto encyclopedia of genes and Genomes(KEGG)signaling pathway.Gene set variation analysis(GSVA)is used to analyze the correlation between RRM2 expression and cell cycle function.Results:The expression of RRM2 in cervical cancer tissues is significantly higher than that in normal tissues(p<0.05).The OS of cervical cancer patients with high RRM2 expression is significantly worse(HR:1.700;p=0.031).The first 1000 genes are significantly positive/negatively correlated with RRM2 by co-expression analysis,among which TCF19,CDCA8 and CENPO are the first three positively correlated genes,and PCMTD1,TP53INP1 and ZNF582 are the first three negatively correlated genes.GO analysis show that these genes are mainly enriched in biological processes such as biological regulation,metabolic processes and stimulus responses.KEGG analysis show that cell cycle,DNA replication,and spliceosomes are significantly enriched signaling pathways.RRM2 expression is positively correlated with cervical cancer cell cycle function,suggesting that RRM2 may promote cervical cancer progression by regulating the cell cycle.Conclusion:RRM2 is up-regulated in cervical cancer and promotes cancer progression,which may play a role

关 键 词：宫颈癌 核糖核苷酸还原酶M2 细胞周期 生物信息学分析 

分 类 号：R737.33[医药卫生—肿瘤]