生信分析宫颈癌脂质代谢酶相关基因表达及功能

Bioconductor analysis of lipid metabolizing enzyme-related gene expression and function in cervical cancer

[目的]基于生信分析宫颈癌脂质代谢酶相关基因的表达及与淋巴结转移和免疫浸润的关系,并构建基因间调控网络。[方法]通过GEO、TCGA和GTEx数据集分析差异基因。检索STRING数据库构建蛋白相互作用(PPI)网络。利用WebGestalt网站对Hub基因进行GO和KEGG途径分析。使用R软件相关性分析获得脂质代谢关键酶相关基因,利用基因表达谱交互分析(GEPIA2)数据库和TIMER 2.0评估脂质代谢酶相关基因的表达水平及其与肿瘤免疫细胞浸润的相关性。最终通过starbase公共数据库构建竞争性内源RNA网络,筛选潜在治疗靶点。[结果]差异分析获得重叠DEGs共121个,利用Cytoscape软件筛选PPI网络共获得10个Hub基因CDC45、KIF2C、CDK1、ASPM、TTK、CDC6、DLGAP5、PLK4、NUF2和BUB1B。使用R软件及其他在线数据库发现,DLGAP5、TTK、BUB1B、ASPM和NUF2基因在宫颈癌中显著上调并分别与脂质代谢关键酶FASN呈显著正相关,且DLGAP5、TTK、BUB1B和ASPM与CD8^(+)T细胞、CD4^(+)T细胞、B细胞和巨噬细胞呈显著负相关;NUF2与CD4^(+)T细胞和B细胞呈显著负相关,最终构建以脂质代谢酶相关基因介导的ceRNA网络。[结论]基于生信分析发现5个脂质代谢酶相关基因在宫颈癌中高表达,其在宫颈癌中与淋巴结转移和多个免疫细胞浸润显著相关,并通过构建ceRNA网络为后续深入研究其影响宫颈癌进展相关机制提供前期基础。

[Objective]To analyze the expression of lipid metabolizing enzyme-related genes in cervical cancer and their relationship with lymph node metastasis and immune infiltration based on biochemical letters,and to construct an intergenic regulatory network.[Method]Differential genes were analyzed by GEO,TCGA,and GTEx datasets.The STRING database was searched to construct protein interaction(PPI)networks.GO and KEGG pathway analysis of Hub genes were performed using the WebGestalt website.Lipid metabolism key enzyme-related genes were obtained using R software correlation analysis,and the expression levels of lipid metabolism enzyme-related genes and their correlation with tumor immune cell infiltration were assessed using the Gene Expression Profile Interaction Analysis(GEPIA2)database and TIMER 2.0.The final competing endogenous RNA networks were constructed through the Starbase public database to screen for potential therapeutic targets.[Result]Differential analysis yielded 121 overlapping DEGs,and screening of the PPI network using Cytoscape software yielded 10 Hub genes CDC45,KIF2C,CDKI,ASPM,TTK,CDC6,DLGAP5,PLK4,NUF2,and BUBIB.using R software and other online databases revealed that DLGAP5,TTK,BUBIB,ASPM,and NUF2 genes were significantly upregulated in cervical cancer and positively correlated with FASN,a key enzyme of lipid metabolism,respectively,and DLGAP5,TTK,BUBIB,and ASPM were negatively correlated with CD8^(+)T cells,CD4^(+)T cells,B cells,and macrophages;NUF2 was negatively corelated with CD4^(+)T cells and B cells.The final construction of a ceRNA network mediated by lipid metabolizing enzyme-related genes.[Conclusion]Based on the raw signal analysis,five lipid metabolizing enzyme-related genes were found to be highly expressed in cervical cancer,and they were significantly associated with lymph node metastasis and multiple immune cell infiltration in cervical cancer,and the construction of ceRNA network provided a preliminary basis for the subsequent in-depth study of their mechanisms affecting cervical cancer progression.