Systematic Pan-Cancer Analysis Identifies CDK1 as an Immunological and Prognostic Biomarker

Abstract

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.

Investigating the effect of polymerase inhibitors on cellular proliferation: Computational studies, cytotoxicity, CDK1 inhibitory potential, and LC‐MS/MS cancer cell entrapment assays

“…On the other hand, cyclin‐dependent kinases (CDKs) are significantly upregulated in multiple types of cancer and their prognosis (Shen et al., 2019; Yang et al., 2022; Zhu et al., 2021). Specially CDK1 is instrumental in variable cell cycle phases and has been widely associated with and is significantly upregulated in HCC (Wu et al., 2018; Ye et al., 2021; Zhao et al., 2013).…”

Development of a novel senescence‐related gene signature to predict clinical outcomes, immune landscape, and chemotherapeutic sensitivity in oral squamous cell carcinoma

“…40 It was also identified as an immunological and prognostic biomarker in multiple cancers. 41 These seven genes have been identified to induce or inhibit cell senescence in diverse cancers. 13,40,[42][43][44][45][46] However, until now, the functional roles of CDK1 in OSCC remain underexplored.…”

Subtype classification based on t cell proliferation-related regulator genes and risk model for predicting outcomes of lung adenocarcinoma

“…Our results of single-cell RNA sequencing analyses and clustering showed that T prolif cells had the highest T cell proliferation scores based on the expression levels of TRPGs among ten types of immune cells. In the original study, most of these TPRGs have been demonstrated to increase the proliferation cancer analysis shows that oncogene CDK1 is an immunological and prognostic biomarker, which may influence tumor immunity mainly by mediating the migration of immune cells to TME, and is positively associated with tumor mutational burden and microsatellite instability (54). CXCL12 is highly enriched in fibroblasts (16).…”

“…For example, TPRGs CDK1 and CXCL12 are expressed in both T cells and various cancer cells. A systematic pan-cancer analysis shows that oncogene CDK1 is an immunological and prognostic biomarker, which may influence tumor immunity mainly by mediating the migration of immune cells to TME, and is positively associated with tumor mutational burden and microsatellite instability ( 54 ). CXCL12 is highly enriched in fibroblasts ( 16 ).…”