Pan-Cancer Landscape of CDK1 Uncovers Its Potential Prognostic Significance and Therapeutic Targeting in Adrenocortical Carcinoma

Background/Aim: Cyclin-dependent kinase 1 (CDK1) is a regulator of the G₂–M transition whose dysregulation undermines cell-cycle fidelity and drives malignant growth. Although CDK1 has been implicated in tumorigenesis, its prognostic value varies by cancer type. Here we analyzed the prognostic landscape of CDK1 across human cancers and prioritized on therapeutic candidates for cancer types in which CDK1 is most strongly implicated.

Materials and Methods: We performed a pan-cancer analysis of CDK1 expression across 31 tumor types from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Project (GTEx), and tested associations with outcome by univariate Cox regression and Kaplan-Meier analysis. To translate these findings into therapeutic insights, we carried out structure-based virtual screening of a curated natural-product library against the CDK1 ATP-binding pocket and assessed predicted binding affinity.

Results: CDK1 was broadly overexpressed across multiple malignancies and high CDK1 expression associated with poorer survival in several tumor cohorts. Adrenocortical carcinoma (ACC) showed one of the strongest and most consistent prognostic associations, with CDK1 expression rising with advancing stage. Structure-based screening nominated five natural compounds namely, Salvianolic acid C, Salvianolic acid A, Calceolarioside B, Chicoric acid, and Plantagoside, as promising CDK1 kinase inhibitors and drug candidates for ACC. These compounds demonstrated favorable CDK1 binding and possess reported biological and anticancer activities, supporting their translational potential.

Conclusion: Our findings highlight CDK1 as a prognostic marker and a therapeutic target across multiple cancers, with particular relevance in ACC. By integrating pan-cancer transcriptomic analysis with structure-based drug discovery, this study not only emphasizes the clinical significance of CDK1 in ACC but also proposes natural compound-derived inhibitors as promising candidates for future therapeutic development.