Yang Yaqi, Liu Qin, Guo Xiyuan, Yuan Qing, Nian Siji, Kang Pengyuan, Xu Zixi, Li Lin, Ye Yingchun
Immune Mechanism and Therapy of Major Diseases of Luzhou Key Laboratory, Public Center of Experimental Technology, School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China.
J Oncol. 2022 Aug 31;2022:8115474. doi: 10.1155/2022/8115474. eCollection 2022.
Cyclin-dependent kinase 1 (CDK1) plays an important role in cancer development, progression, and the overall process of tumorigenesis. However, no pan-cancer analysis has been reported for CDK1, and the predictive role of CDK1 in immune checkpoint inhibitors (ICIs) therapy response remains unexplored. Thus, in this study, we first investigated the potential oncogenic role of CDK1 in 33 tumors by multidimensional bioinformatics analysis based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Bioinformatic analysis and immunohistochemical experiments confirmed that CDK1 is significantly upregulated in most common cancers and is strongly associated with prognosis. Further analysis indicated that CDK1 may influence tumor immunity mainly by mediating the degree of tumor infiltration of immune-associated cells, and the effect of CDK1 on immunity is diverse across tumor types in tumor microenvironment. CDK1 was also positively correlated with tumor mutational burden (TMB) and microsatellite instability (MSI) in certain cancer types, linking its expression to the assessment of possible treatment response. The results of the pan-cancer analysis study showed that the CDK1 gene was positively associated with the expression of three classes of RNA methylation regulatory proteins, and affects RNA function through multiple mechanisms of action and plays an important role in the posttranscriptional regulation of the tumor microenvironment. These findings shed light on the role of the CDK1 gene in cancer progression and provide information to further study the CDK1 gene as a potential target for pan-cancer.
细胞周期蛋白依赖性激酶1（CDK1）在癌症发展、进展以及肿瘤发生的整个过程中发挥着重要作用。然而，尚未有关于CDK1的泛癌分析报道，并且CDK1在免疫检查点抑制剂（ICI）治疗反应中的预测作用仍未得到探索。因此，在本研究中，我们首先基于癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）数据集，通过多维生物信息学分析研究了CDK1在33种肿瘤中的潜在致癌作用。生物信息学分析和免疫组织化学实验证实，CDK1在大多数常见癌症中显著上调，并且与预后密切相关。进一步分析表明，CDK1可能主要通过介导免疫相关细胞的肿瘤浸润程度来影响肿瘤免疫，并且CDK1在肿瘤微环境中对免疫的影响因肿瘤类型而异。在某些癌症类型中，CDK1还与肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）呈正相关，将其表达与可能的治疗反应评估联系起来。泛癌分析研究结果表明，CDK1基因与三类RNA甲基化调节蛋白的表达呈正相关，并通过多种作用机制影响RNA功能，在肿瘤微环境的转录后调控中发挥重要作用。这些发现揭示了CDK1基因在癌症进展中的作用，并为进一步研究CDK1基因作为泛癌潜在靶点提供了信息。
