Department of Infectious Diseases, Binzhou Medical University Hospital, Binzhou, 256600, Shandong, China.
Department of General Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, 110000, Liaoning, China.
Eur J Med Res. 2024 May 8;29(1):272. doi: 10.1186/s40001-024-01869-6.
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.
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.
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.
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.
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，已被证明在多种肿瘤中具有致癌特性。然而，目前还没有针对 CDKN3 的泛癌分析。
使用生物信息学工具，如癌症基因组图谱（TCGA）和 UCSC Xena 数据库，对 CDKN3 进行了全面的泛癌分析。该研究调查了 CDKN3 在 33 种不同肿瘤中的功能，以及基因表达、生存预后状态、临床意义、DNA 甲基化、免疫浸润和相关信号通路的研究。
CDKN3 在大多数肿瘤中显著上调，并与患者的总生存（OS）相关。CDKN3 的甲基化水平在肿瘤和正常组织之间有显著差异。此外，在各种肿瘤中，CD4+T 细胞、癌症相关成纤维细胞、巨噬细胞和内皮细胞的浸润与 CDKN3 的表达相关。从机制上讲，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有关。
本研究中的泛癌分析提供了对 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 可能为肿瘤的治疗提供新的治疗策略。
