CSNK2B Expression Aligns with a GDF15-Associated Immune Molecular State in Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) remains a major cause of cancer-related mortality, and responses to immune checkpoint blockade are often limited. Casein kinase 2 beta (CK2beta), encoded by CSNK2B, has established tumor-intrinsic functions, but its relationship with immune states in HCC remains unclear. Methods: We integrated TCGA-LIHC, six GEO cohort-platform combinations, GSE149614 single-cell RNA sequencing data, CIBERSORTx deconvolution, broad-compartment CellChat inference, and public proteomic resources. We evaluated CSNK2B expression, overall survival, a prespecified GDF15-associated Treg/checkpoint transcriptional module, tumor microenvironment features, compartment-level localization, and protein-level support. Results: CSNK2B was upregulated in TCGA-LIHC and all six external cohort-platform comparisons but was not a robust prognostic marker. The strongest immune association was with the GDF15-associated Treg/checkpoint module (Spearman rho = 0.371, q = 2.9 × 10−12); the direction was positive in all six GEO analyses and four passed BH-FDR. Deconvolution results were small and heterogeneous. CSNK2B and GDF15 were most prominent in hepatocyte-like compartments, while the candidate hepatocyte-to-T/NK GDF15–TGFBR2 pair was not reproduced in pooled data or in any of 10 patient-stratified CellChat runs. Public proteomic datasets supported tumor-side elevation of both proteins. Conclusions: CSNK2B expression aligns with a reproducible GDF15-associated transcriptional state in HCC, accompanied by selective stromal, endothelial, and immune-context changes. The evidence is associative and provides hypotheses for perturbation, spatial, and co-culture validation rather than a causal or treatment-prediction claim.