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Tumor Discovery CK2 deregulation in non-small-cell lung cancer

A B

C D

Figure 6. Quantification of IHC results in LUAD and LUSC samples using the combined IHC score. (A) Ratio (R) of tumor (T)/para-neoplastic (PN)
positive staining (R = T/PN) as an indicator for tumor-specific association. The analysis included all positive (+/++/+++) or positive-to-strong positive
intensity samples (++/+++); (B) Percentage of all positive or positive-to-strong positive staining in LUAD or LUSC samples; (C) IHC results for total AKT
protein and phosphorylated AKTs129 protein (pAKT) in LUAD and LUSC samples; (D) Visualization of correlations between CSNK2A1/CSNK2A2/
CSNKB protein subunit levels and phosphorylated AKTs129. Statistical analysis is detailed in Tables S3 and S4.
Abbreviations: IHC: Immunohistochemistry; LUAD: Lung adenocarcinoma; LUSC: Lung squamous carcinoma.
efficacy of CK2 inhibition as an anticancer strategy may be LUAD cohorts. Promoter/1stExon methylation showed a
context-dependent. 13 weak (<−0.30) negative correlation with CSNK2A2 and
Despite the availability of clinical multiomics databases, CSNK2B mRNA levels. Interestingly, CSNK2A1 mRNA
there is no comprehensive analysis encompassing CK2 overexpression was nearly twice as common as that of
mutational burden, gene/protein expression, and, CSNK2A2 and CSNK2B, with higher median expression
values, particularly in LUSC samples. However, differential
importantly, CK2 enzymatic activity deregulation in
cancer. CK2 subunit-specific contributions to certain methylation alone does not fully explain the extensive
tumor phenotypes highlight the necessity for analyzing deregulation of CSNK2 mRNA observed in NSCLC,
suggesting that more complex transcriptional and post-
each subunit’s regulatory patterns and functional 3
implications individually. 28-30 Such analyses may provide transcriptional regulatory mechanisms are involved.
fresh insights for the CK2 research community, which A meta-analysis of 20 LUAD and 17 LUSC clinical
continues to debate whether CK2 is an actionable and safe studies corroborated that CSNK2A1 and CSNK2B mRNA
target for cancer intervention. 6,8 overexpression correlates with poorer prognosis in LUAD,
whereas CSNK2A2 overexpression is associated with
In this study, we used cBioPortal to analyze a pan-
cancer dataset and two NSCLC cohorts from the TCGA better outcomes. This trend for CSNK2B and CSNK2A2
was previously observed in a microarray-based study.
26
PanCancer Atlas. Our results indicate that mutational Overall, we found that CSNK2A1 and CSNK2B mRNA
events, such as single base insertions, substitutions, levels were particularly elevated in primary LUAD and
deletions, and/or can, are rare within CSNK2 subunit genes LUSC samples, as well as in a limited set of metastatic
and, when present, do not appear to confer oncogenic NSCLC clinical samples. In addition, we identified direct
potential. These findings align with CK2’s roles in the correlations between CSNK2 subunit mRNA levels and
concept of “non-oncogene addiction”. 1 tumor infiltration by MDSC/CAF. In LUAD, the strongest
The CSNK2 gene promoters display characteristics correlations were observed between CSNK2A1 and MDSC
typical of housekeeping genes, including a CpG island infiltration, as well as between CSNK2B and MDSC
near exon 1, which can be methylated. Therefore, we infiltration. These cell populations, known for their array
31
investigated promoter/1stExon/5’UTR methylation and of tumor-supportive functions, rely on secreted molecules
its correlations with CSNK2 gene expression in LUSC and and mediators, including CK2 substrates, for their

Volume 3 Issue 4 (2024) 10 doi: 10.36922/td.4571