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




            A



















            B                                                    C















            Figure 2. Oncoprint analysis of genetic alterations contained in LUAD and LUSC cohorts. (A) Only samples with mutations, CNA, and mRNA expression
            data were included (LUAD = 503; LUSC = 466); (B) LUAD samples with mutations and CNA data only (n = 507); (C) LUSC samples with mutations and
            CNA data only (n = 469). All annotations and analyses were obtained from cBioPortal, as described in the materials and methods section.
            Abbreviations: LUSC: Lung squamous cell carcinoma; LUAD: Lung adenocarcinoma; CAN: Copy-number alterations.


            frequency of <1.5% across the cohort. In addition, CNA   CSNK2A2 mRNA expression in both LUAD (Spearman:
            events were uncommon, with amplifications and deletions   0.14;  P  = 1.214e-3) and LUSC (Spearman: 0.24;
            found in only 3 – 4% of samples (Figure 2B and C). As in the   P  = 1.39e-7). However, no significant correlations
            pan-cancer cohort, these CNAs corresponded roughly with   were found between the catalytic subunits (CSNK2A1/
            target gene expression (Figure S2).                CSNK2A2) and regulatory subunit  CSNK2B at the
              Despite the limited impact of mutations and CNAs   mRNA expression level in these NSCLC subtypes (data
            on  individual  CSNK2  subunits,  mRNA  overexpression   not shown).
            was  prevalent  across  analyzed  LUAD  and  LUSC    To investigate potential regulatory mechanisms, we
            cohorts  (Figure  2A).  Particularly,  CSNK2A1  mRNA   analyzed methylation data for putative correlations between
            deregulation was found in over 90% of LUSC samples   CSNK2A1-TSS200,     CSNK2A2-TSS1500/1rstExon,
            and 70% of LUAD samples. Overall, catalytic subunit   and   CSNK2B-TSS1500/1stExon/5’UTR  methylation
            deregulation was more prominent in LUSC than LUAD.   and mRNA expression levels of  CSNK2 subunits.
            While  CSNK2A1 consistently showed overexpression,   n LUAD, we found weak negative correlations for
            CSNK2A2 mRNA levels varied, with both elevated and   CSNK2A2-TSS1500 (Spearman: −0.15;  P = 8.658e-4)
            reduced expression relative to normal-matched tissues.   and   CSNK2B-TSS1500/1stExon/5’UTR  (Spearman:
            For  CSNK2B, overexpression was much more common   −0.14; P = 1.528e-3) (Figure S3A). Similarly, methylation
            than downregulation, with over 40% of LUAD and LUSC   of  CSNK2A2 and  CSNK2B on promoter regions, but
            samples displaying higher mRNA levels compared to   not CSNK2A1, correlated with mRNA expression in
            normal-matched tissues (Figure 2A).                LUSC  samples,  with significant  signals  observed  for
              As in the pan-cancer cohorts,  CSNK2A1 mRNA      CSNK2A2-TSS1500 (Spearman: −0.09;  P = 0.0443),
            expression showed a weak positive correlation with   CSNK2A2-1rstExon (Spearman: −0.10;  P = 0.0368), and


            Volume 3 Issue 4 (2024)                         5                                 doi: 10.36922/td.4571
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