皮肤黑素瘤中细胞分裂周期相关蛋白8的表达水平及功能学分析  

Expression level and functional analysis of cell division cycle associated protein 8 in cutaneous melanoma

作　　者：袁涛 江佳慧 陈楠 张元林 苏豆 孟秀梅 唐彪[1] 何彩凤[1] 卢晓红 慈超 Yuan Tao;Jiang Jiahui;Chen Nan;Zhang Yuanlin;Su Dou;Meng Xiumei;Tang Biao;He Caifeng;Lu Xiaohong;Ci Chao(Department of Dermatology,Yijishan Hospital,Wannan Medical College,Wuhu,Anhui 241004,China)

机构地区：[1]皖南医学院弋矶山医院皮肤科,安徽芜湖241004

出　　处：《齐齐哈尔医学院学报》2024年第3期207-211,共5页Journal of Qiqihar Medical University

基　　金：2022年度皖南医学院校中青年科研项目(WK2022F17);2022年度皖南医学院校重点科研项目(WK2022F17);安徽省高校科学研究重大项目(KJ2021ZD0097);2023年安徽省自然科学基金青年基金(2308085QH269)。

摘　　要：目的基于生物信息学方法分析CDCA8在皮肤黑素瘤组织中的表达水平及其相关生物学功能。方法TCGA数据库中下载皮肤黑素瘤数据集,分析CDCA8在皮肤黑素瘤组织中的表达,K-M曲线分析皮肤黑素瘤组织中CDCA8表达水平与总体生存率的关系,UALCAN数据库筛选皮肤黑素瘤中与CDCA8的共表达基因,并对共表达基因进行GO和KEGG富集分析。TIMER数据库分析皮肤黑素瘤组织中CDCA8与免疫细胞浸润的相关性。HPA数据库验证CDCA8在皮肤黑素瘤组织及正常组织中的表达差异。结果与正常组织相比,CDCA8在皮肤黑素瘤组织中明显高表达(P<0.5);与皮肤黑素瘤TP-53野生型相比,CDCA8表达水平在TP-53突变型中明显升高(P<0.05)。皮肤黑素瘤中CDCA8高表达组总体生存率显著低于CDCA8低表达组(HR=1.500,P=0.005)。皮肤黑素瘤组织中CDCA8共表达基因主要富集于细胞核、细胞质、细胞分裂、细胞周期、DNA修复、蛋白结合、RNA结合、细胞周期、DNA复制及细胞核质转运等过程。皮肤黑素瘤中CDCA8与B细胞(r=0.166,P<0.001)、CD8^(+)T细胞(r=0.176,P<0.001)、中性粒细胞(r=0.193,P<0.001)及树突状细胞(r=0.230,P<0.001)浸润程度存在显著正相关性。免疫组化显示CDCA8在皮肤黑素瘤组织中均呈现高强度表达,而在正常组织中无表达或低表达。结论CDCA8在皮肤黑素瘤组织中呈现高表达状态,与患者不良预后显著相关,CDCA8可能通过调控细胞周期及免疫细胞浸润参与皮肤黑素瘤的发病机制。Objective To analyze the expression level of cell division cycle associated protein 8(CDCA8)and its related biological functions in cutaneous melanoma by bioinformatics method.Methods The data set of skin melanoma was downloaded from the TCGA database to analyze the expression level of CDCA8 in skin melanoma tissues.The relationship between CDCA8 expression level and overall survival rate was analyzed by K-M curve.The co-expression genes of CDCA8 in skin melanoma were screened by UALCAN database.The co-expressed genes of CDCA8 in skin melanoma were performed by GO and KEGG enrichment analysis.The correlation between CDCA8 and immune cell infiltration in skin melanoma was analyzed by TIMER database.The HPA database was used to verify the CDCA8 expression level difference between skin melanoma tissue and normal tissue.Results Compared with normal tissues,the expression level of CDCA8 in cutaneous melanoma tissues was significantly increased(P<0.5).The expression level of CDCA8 in TP-53 mutant cutaneous melanoma was significantly increased compared with TP-53 WT(P<0.5).The overall survival rate in CDCA8 high expression group was significantly lower than that in CDCA8 low expression group(HR=1.500,P=0.005).The co-expressed genes of CDCA8 in cutaneous melanoma were mainly enriched in nucleus,cytoplasm,cell division,cell cycle,DNA repair,protein binding,RNA binding,cell cycle,DNA replication and cytoplasmic transport.In cutaneous melanoma,CDCA8 was positively correlated with the degree of infiltration of B cells(r=0.166,P<0.001),CD8^(+)T cells(r=0.176,P<0.001),neutrophils(r=0.193,P<0.001)and dendritic cells(r=0.230,P<0.001).Immunohistochemistry showed that CDCA8 was highly expressed in cutaneous melanoma tissues,while no expression or low expression in normal cutaneous tissues.Conclusions The CDCA8 is highly expressed in cutaneous melanoma tissues,which is significantly associated with poor prognosis of patients.The CDCA8 may be involved in the pathogenesis of cutaneous melanoma by regulating cell cycle and immune cell

关 键 词：皮肤黑素瘤 细胞分裂周期相关蛋白8 预后 免疫微环境 

分 类 号：R739.5[医药卫生—肿瘤]