细胞周期蛋白依赖性激酶抑制蛋白2A与肾细胞癌患者临床及预后指标相关性研究

Correlation between cyclin-dependent kinase inhibitor 2A and clinical and prognostic indicators in patients with renal cell carcinoma

目的探讨细胞周期蛋白依赖性激酶抑制蛋白2A(CDKN2A)与肾细胞癌(RCC)各参数的相关性。方法在TCGA数据库中筛选出差异表达基因CDKN2A,并在TCGA数据库中验证CDKN2A的表达以及与RCC患者预后情况的相关性。采用Cox回归法进行多因素分析,然后在此基础上构建列线图,进行内部验证。在TIMER数据库中分析CDKN2A与免疫细胞之间的相关性。采用GSEA富集分析,探讨可能的作用机制。结果数据库筛选得到差异表达分子为CDKN2A,CDKN2A在癌组织中的表达高于癌旁组织。TCGA和KM-plotter数据库显示,CDKN2A低表达的RCC患者有更好的预后。列线图C-指数为0.749(0.721~0.776),预测模型具有较好的准确性。TIMER数据库显示CDKN2A的表达与免疫浸润显著相关。结论CDKN2A的表达降低可以显著延长RCC患者的总体生存期、疾病特异性生存期和无进展间隔期,可以用作RCC的新型预测性生物标志物,同时,可能与RCC的免疫浸润相关,在RCC微环境中对于肿瘤细胞发生免疫逃逸可能起重要的促进作用。干扰CDKN2A可能通过参与TP53调节RCC的周期阻滞,从而改善RCC的预后。这些发现为RCC抗癌策略的开发提出潜在的靶点。

Objective To explore the correlation between cyclin-dependent kinase inhibitor 2A(CDKN2A)and renal cell carcinoma(RCC).Methods Differential expression genes CDKN2A were screened from TCGA database,and verified the expression of CDKN2A and its correlation with the prognosis of patients with RCC in the TCGA database.Cox regression method was used for multivariate analysis,and then a nomogram was constructed on this basis for internal verification.The correlation between CDKN2A and immune cells was analyzed in timer database.GSEA enrichment analysis was used to explore the possible mechanism.Results The differential expression molecule was CDKN2A,and the expression of CDKN2A in cancer tissues was higher than that in adjacent tissues.TCGA and KM-plotter databases showed that RCC patients with low expression of CDKN2A had better prognosis.The c-index of nomogram is 0.749(0.721-0.776),and the prediction model has good accuracy.The timer database showed that the expression of CDKN2A was significantly correlated with immune infiltration.Conclusions The reduced expression of CDKN2A can significantly prolong the overall survival,progression free interval and disease specific survival of RCC patients,and can be used as a new predictive biomarker of RCC.At the same time,it may be related to the immune infiltration of RCC,and may play an important role in promoting the immune escape of tumor cells in the RCC microenvironment.Interference with CDKN2A may regulate the cycle arrest of renal cell carcinoma by participating in TP53,thereby improving the prognosis of RCC.These findings provide a potential target for the development of RCC anticancer strategies.