Deregulation of Casein Kinase-2 in non-small-cell lung cancer: A subunit-specific analysis

Abstract

Casein kinase-2 (CK2) is a constitutively active kinase that supports neoplastic properties. Although there is an extensive body of preclinical research on CK2, translational and clinical information remains limited and sparse. In this study, we interrogated clinical multiomics databases to examine CK2 deregulation across various cancers. Specifically, we analyzed the mutational frequency, copy-number alterations (CNA), and mRNA expression of CK2 catalytic (CSNK2A1 and CSNK2A2) and regulatory (CSNK2B) subunits across two major cancer genomic repositories (The Cancer Genome Atlas/International Cancer Genome Consortium). These genomic and transcriptomic analyses were further focused on lung cancer and complemented by in situ assessments of CK2 protein subunits and enzymatic activity in biopsies from non-small-cell lung cancer (NSCLC). Our findings indicate that gene mutations and CNA do not account for the elevated mRNA levels and enzymatic activity of CK2 subunits in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Particularly, the upregulation of CSNK2A1 and CSNK2B mRNA was associated with a worse prognosis and showed a direct correlation with the infiltration of myeloid-derived suppressor cells in LUAD. At the protein levels, all CK2 subunits and enzymatic activity were markedly elevated in LUAD (n = 103) and LUSC (n = 31) biopsies; however, only CSNK2A1 expression correlated positively with tumor size and disease stage. Finally, CSNK2A1 appeared to be more tumor-specific than CSNK2A2, suggesting that targeted therapies against this catalytic subunit or its homotetramer may offer a more favorable therapeutic window in NSCLC.