CKS2 and Its Interacting Network Induce Tumor Progression with Adverse Effects on Patients Survival in a Pan-Cancer Model

Abstract

Background: Cyclin-dependent kinases regulatory subunit 2 (CKS2) has an essential biological function as it binds to the cyclin-dependent kinases catalytic site, which in turn regulates the cell cycle. Hence, malfunction of CKS2 can be finally translated as an irregular cell cycle and malignancy progression. The current study aimed to comprehensively analyze the oncogenic roles of CKS2 in a pan-cancer model focusing on the interference of CKS2 expression with the infiltration of different immune components in the tumor microenvironment. Methods: Here, we applied a comprehensive bioinformatics analysis based on the available data in different databases to investigate the expression levels and the genetic, and epigenetic modifications that occurred to CKS2 and checked the possible correlation of those events with the abundance of immune factors with variable functions. Results: CKS2 was found to be overexpressed in multiple human cancers and that resulted in cancer progression in terms of stage and grade in addition to shorter patients survival under different models. Enhanced infiltration and release of Myeloid-derived suppressor cell (MDSC) and Chemokine ligand 8 (CCL8) with the opposite trend in Natural killer (NK) cells and CCL14 correlated to CKS2 expression was detected as a potential immunological mechanism of CKS2 cancer progression induction. Additionally, the interaction network revealed cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinases regulatory subunit 1B (CKS1B), cell division cycle protein 20 (CDC20), G2/Mitotic-Specific Cyclin-B1 (CCNB1), and G2/Mitotic-Specific Cyclin-B2 (CCNB2) as proteins closely associated with CKS2, where that network represented the molecular mechanism for CKS2 tumor induction. Conclusions: Collectively, the current study nominates CKS2 and a potential biomarker and therapeutic target in a pan-cancer model.