CDCA5在皮肤恶性黑色素瘤中的表达及其与预后相关性的生物信息学分析

The expression of CDCA5 gene in cutaneous malignant melanoma and its correlation with prognosis of the patients by bioinformatic analysis

目的:探讨CDCA5在皮肤恶性黑色素瘤(cutaneous malignant melanoma,CMM)中的表达、相关信号通路及其与患者预后之间的关系。方法:应用Oncomine和GEPIA数据库研究CDCA5基因在不同肿瘤组织中的表达情况以及与患者预后关系。此外,还收集了我院41例黑色素瘤患者及41例正常皮肤病例进行免疫组化分析。cBioPortal数据库用于研究CDCA5基因突变情况。应用STRING数据库构建CDCA5相关蛋白-蛋白相互作用网络,并进行功能富集和通路分析。应用TISIDB数据库探究CDCA5与免疫浸润的关系。结果:CDCA5基因在大多数肿瘤组织包括CMM中的表达水平上调,高表达与患者的预后不良有关。免疫组化结果显示,CDCA5在CMM中表达也是明显高于正常皮肤组织。TCGA数据库中有8%的CDCA5基因在CMM组织中发生了突变。CDCA5相关蛋白-蛋白相互作用网络中,相互作用蛋白网络富集明显(P<1.0E-16)。CDCA5编 码蛋白的分子功能主要为蛋白质结合、染色体结合、ATP结合以及蛋白激酶活性等。而生物学过程主要集中于姐妹染色单体凝聚力、有丝分裂核分裂、细胞分裂等。KEGG信号通路主要为细胞周期、卵母细胞减数分裂和孕激素介导的卵母细胞成熟。GSEA结果显示CDCA5相关显著变化的通路主要为炎症反应、TNFα-NF-κB通路、干扰素alpha通路、干扰素gamma通路、IL2-STAT5通路、IL6-JAK-STAT3通路、p53通路以及KRAS通路。此外,CDCA5基因与活化CD4^(+)T细胞成正相关,与不成熟B细胞、肥大细胞、1型辅助T细胞以及效应记忆CD8^(+)T细胞成负相关。结论:CDCA5在CMM患者肿瘤组织中表达较高,高表达与患者的预后不良有关。

Objective:To explore the expression and signaling pathway of CDCA5 in cutaneous malignant melanoma(CMM)and its correlation with prognosis of CMM patients.Methods:Oncomine and TCGA databases was used to investigate the expression of CDCA5 gene in different tumor tissues.GEPIA was applied to identify the relationship between CDCA5 and prognosis of CMM patients.In addition,41 CMM and 41 normal tissues were collected for immunohistochemical(IHC)staining and evaluation.cBioPortalwas used to identify the mutation of CDCA5 in CMM.The STRING database was utilized to construct a protein-protein interaction(PPI)network,and the DAVID database and GSEA were used to perform functional enrichment and pathway analysis.TISIDB database was used to explore the relationship between CDCA5 and immune infiltration.Results:The expression level of CDCA5 gene was up-regulated in most tumor tissues,and the expression of CDCA5 in CMM was significantly higher than in normal skin tissues,which indicatedworse prognosis of CMM patients.IHC results showed increased expression of CDCA5 in CMM compared to normal tissues.Based on the data from TCGA database,8%of the CDCA5 gene was mutated in CMM.In the PPI network,the enrichment of the interacting protein network is obvious(P<1.0E-16).The molecular functions were mainly protein binding,chromosome binding,ATP binding and protein kinase activity.The biological process was mostly focused on sister chromatid cohesion,mitotic nuclear division and cell division.The KEGG signaling pathway was primarily the cell cycle,oocyte meiosis and progesterone-mediated maturation of oocytes.GSEA results showed the significantlyinvolved hallmarks were inflammation,TNFa-NF-κB pathway,interferon alpha pathway,interferon gamma pathway,IL2-STAT5 pathway,IL6-JAK-STAT3 pathway,p53 pathway and KRAS pathway.CDCA5 gene was also positively correlated with activated CD4^(+)T cells,while negatively correlated with immature B cells,mast cells,type 1 helper T cells and effect memory CD8^(+)T cells.Conclusion:CDCA5 is highly expressed in CMM and is closely related to the poor prognosis.