背景:细胞周期蛋白依赖性激酶抑制剂蛋白3(CDKN3),作为蛋白激酶家族的一员,已被证明在几种肿瘤中表现出致癌特性。然而,没有对CDKN3的泛致癌分析。
方法:使用生物信息学工具,如癌症基因组图谱(TCGA)和UCSCXena数据库,对CDKN3进行了全面的泛癌症分析.倒置包括对33种不同类型肿瘤的CDKN3功能的检查,以及基因表达的探索,生存预后状态,临床意义,DNA甲基化,免疫浸润,和相关的信号通路。
结果:CDKN3在大多数肿瘤中显著上调,并与患者的总生存期(OS)相关。CDKN3的甲基化水平在肿瘤和正常组织之间显著不同。此外,CD4+T细胞浸润,癌症相关成纤维细胞,巨噬细胞,内皮细胞与CDKN3表达相关。机械上,CDKN3与P53、PI3K-AKT、细胞周期检查点,有丝分裂纺锤体检查点,和染色体维持。
结论:我们在研究中进行的泛癌症分析提供了对CDKN3基因在肿瘤发生中的参与的全面理解。研究结果表明,靶向CDKN3可能会导致治疗肿瘤的新治疗策略。
BACKGROUND: Cell cycle protein-dependent kinase inhibitor protein 3 (CDKN3), as a member of the protein kinase family, has been demonstrated to exhibit oncogenic properties in several tumors. However, there are no pan-carcinogenic analyses for CDKN3.
METHODS: Using bioinformatics tools such as The Cancer Genome Atlas (TCGA) and the UCSC Xena database, a comprehensive pan-cancer analysis of CDKN3 was conducted. The inverstigation encompassed the examination of CDKN3 function actoss 33 different kinds of tumors, as well as the exploration of gene expressions, survival prognosis status, clinical significance, DNA methylation, immune infiltration, and associated signal pathways.
RESULTS: CDKN3 was significantly upregulated in most of tumors and correlated with overall survival (OS) of patients. Methylation levels of CDKN3 differed significantly between tumors and normal tissues. In addition, infiltration of CD4 + T cells, cancer-associated fibroblasts, macrophages, and endothelial cells were associated with CDKN3 expression in various tumors. Mechanistically, CDKN3 was associated with P53, PI3K-AKT, cell cycle checkpoints, mitotic spindle checkpoint, and chromosome maintenance.
CONCLUSIONS: Our pan-cancer analysis conducted in the study provides a comprehensive understanding of the involvement of CDKN3 gene in tumorigenesis. The findings suggest that targeting CDKN3 may potentially lead to novel therapeutic strategies for the treatment of tumors.