CDKN2A基因突变与肾细胞癌药物敏感性和预后的关系

Relationship Between CDKN2A Gene Mutation and Drug Sensitivity and Prognosis of Renal Cell Carcinoma

目的明确CDKN2A突变状态对肾癌进展机制及药物敏感性的影响。方法使用开源网络工具cBioPortal分析肾癌患者CDKN2A突变类型、频率及生存状况(总体生存和无疾病生存),采用GDSC平台绘制关于CDKN2A的药物敏感火山图和散点图,基因集富集分析(GSEA)评估预定义基因集中的基因分布,绘制差异表达基因(DEGs)和DEGs火山图。结果TCGA数据显示,5.00%的肾细胞癌存在CDKN2A突变,CDKN2A突变的肾细胞癌患者总体生存率和无病生存率较差;CDKN2A突变可能会增加对Tenovin-6等药物的耐药性,这在各种肿瘤和肾细胞癌中的野生型具有显著的选择性。GO和KEGG分析显示,DEGs在与细胞分裂和多种代谢进展相关的通路中富集。结论多个基因和通路途径可能在CDKN2A突变中起关键作用。

Objective To clarify the effect of CDKN2A mutation status on the progression mechanism and drug sensitivity of renal cell carcinoma.Methods The open source network tool cBioPortal was used to analyze the mutation type,frequency and survival status(overall survival and disease-free survival)of CDKN2A in patients with renal cell carcinoma.The GDSC platform was used to draw the drug-sensitive volcano map and scatter plot of CDKN2A.The gene set enrichment analysis(GSEA)was used to evaluate the gene distribution in the predefined gene set,and the differentially expressed genes(DEGs)and DEGs volcano map were drawn.Results TCGA data showed that 5.00%of renal cell carcinoma had CDKN2A mutation,and the overall survival and disease-free survival of patients with CDKN2A mutation were poor.CDKN2A mutations might increase resistance to drugs such as Tenovin-6,which was significantly selective for wild-type in various tumors and renal cell carcinoma.GO and KEGG analysis showed that DEGs were enriched in pathways associated with cell division and multiple metabolic processes.Conclusion Multiple genes and pathways may play a key role in CDKN2A mutation.