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微型染色质维持蛋白家族在人类食管癌发生发展中的影响 被引量:3

Minichromosome maintenance proteins are novel biomarkers of human esophageal cancer
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摘要 目的目前关于食管癌组织中微型染色质维持蛋白(MCMs)家族成员的表达情况及作用机制尚不明确。文章通过生物信息工具分析微型染色质维持蛋白(MCMs)家族成员在食管癌中的表达情况以及对食管癌发生发展过程的影响,旨在发掘与探索MCMs在临床食管癌早期诊断和预防中的价值。方法利用生信数据库分析MCMs家族基因在食管癌患者中的表达情况,同时进行食管癌患者MCMs家族基因间的共表达分析;利用人类蛋白图谱分析MCMs在食管粘膜组织中的蛋白表达情况;利用cBioPortal在线工具分析食管癌患者MCMs家族基因的突变情况并找到其共表达基因;利用STRING软件构建MCMs家族与其相邻基因的蛋白质相互作用模型,最后进行基因本体功能(GO)以及京都基因与基因百科全书(KEGG)信号通路的富集分析。结果在Su和Hu数据集的食管鳞状细胞癌子集中表达增高,增高的倍数分别为2.717,4.186。MCM3在Hu的数据集的食管鳞状细胞癌数据子集中表达增高,增高倍数为2.159。MCM4在Hu和Su数据集的食管鳞癌数据子集中表达增高,增高倍数为2.292,2.554。MCM5在Su和Hu数据集的食管鳞癌子集中表达增高,增高倍数分别为2.354,2.419。MCMs家族成员在食管癌中的共表达情况分析表明MCMs各家族成员的表达在食管癌组织中具有相关性(P<0.05,R>0.4)。人类蛋白图谱的正常食管粘膜组织MCMs家族蛋白均呈现低表达现象,与生信数据库的结果相一致。该家族基因表达预后分析仅MCM4,MCM6与食管癌患者预后具有相关性。MCMs家族成员在食管癌患者中的基因改变形式主要包括扩增,突变和多重基因改变3种。GO分析结果表明,MCMs家族及其相邻基因的功能主要聚集在DNA的复制过程,MCMs复合体结构组成和DNA复制源的结合等多个方面。KEGG信号通路分析结果显示MCMs家族及其相邻基因主要聚集在DNA复制,细胞周期,错配修复和核酸切除修复等4个关键通路。结论MCMs家族成员在食管癌患者中呈现高表达现象,MCM4,MCM6的表达情况与食管癌患者预后相关,其改变可能参与DNA复制,MCMs复合体组成及细胞周期等生物过程从而影响食管癌进展。 Objective In this paper,we used biological information methods to analyze the expression of minichromosome maintenance proteins(MCMs)in human esophageal cancer tissues and the effect on development and progress of cancer.We aimed to investigate and explore the value of MCMs in early diagnosis and clinical treatment of esophageal cancer.Methods We used various bioinformatics databases to analyze the expression of MCMs in esophageal cancer tissues.Meanwhile,co-expression of all MCMs members in esophageal cancer was also analyzed.Then,we used human protein profiles to analyze the expression of MCMs in normal human esophageal tissues.After that,we used cBioPortal online tools to analyze mutation of MCMs in esophageal cancer and found its co-expression genes.Besides,we used STRING software to construct an interaction model among MCMs members and their neighboring genes.At last,the GO and KEGG Pathway enrichment analysis were also carried out.Results The expression of MCMs in esophageal cancer tissues enhanced significantly compared with normal esophageal tissues.In human protein profiles,it appeared a low expression of MCMs members in normal esophageal tissues,which was consistent with the predicted results of bioinformatics database.Only MCM4 and MCM6 were correlated with prognosis of esophageal cancer patients.There were three mutational patterns of MCMs in esophageal cancer including amplification,mutation and multiple gene alteration.GO analysis revealed that function of MCMs and their neighboring genes mainly focused on the DNA replication process,composition of MCMs complex and combination with DNA replication initiation.Meanwhile,KEGG analysis revealed it mainly focused on the DNA replication process,cell cycle,DNA mismatch repair system and nucleic acid excision repair.Conclusion There was a high expression of MCMs in esophageal cancer.Moreover,the expression of MCM4 and MCM6 were correlated with prognosis of esophageal cancer patients.MCMs were involved in various important biological processes such as DNA replication process,composition of MCMs complex and cell cycle,which may contribute to the development of esophageal cancer.
作者 王利 刘丹薇 WANG Li;LIU Dan-wei(Department of Clinical Laboratory,Nanjing Second Hospital,Affiliated to Nanjing University of Traditional Chinese Medicine,Nanjing 210003,Jiangsu,China;Transfusion Department,Second Peoples′Hospital of Changzhou City,Changzhou 213003,Jiangsu,China)
出处 《医学研究生学报》 CAS 北大核心 2021年第8期815-822,共8页 Journal of Medical Postgraduates
关键词 微型染色质维持蛋白家族 食管癌 基因改变 富集分析 minichromosome maintenance proteins esophageal cancer genetic alteration enrichment analysis
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