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




            A                                                 B























            C                                                 D





















            Figure 3. Meta-analysis of CSNK2 mRNA expression versus overall survival, encompassing 20 independent LUAD and LUSC tumor data cohorts. Hazard
            ratios for each CSNK2 gene were independently assessed across studies. Summary statistics and the global score are displayed at the bottom left and right
            corners of the charts, respectively. Hazard profiles for CSNK2A1 and CSNK2B are shown for (A and C) LUAD and (B and D) LUSC.
            Abbreviations: LUSC: Lung squamous cell carcinoma; LUAD: Lung adenocarcinoma.

              To quantify AKTs129 phosphorylation as an indicator   Further IHC analysis was conducted on a subset of
            for CK2 enzymatic activity  in situ, we performed IHC   LUAD (n = 66) and LUSC (n = 16) samples to quantify
            analysis using a phosphosite-specific antibody on a subset   NPM1s125 phosphorylation as a second in situ indicator
            of LUAD (n = 76) and LUSC (n = 36) samples from the   of CK2 enzymatic activity (Figure S9). Both total NPM1
            same patient cohort (Tables S3 and S4). Both total protein   protein and phosphorylated NPM1s125 protein (pNPM1)
            levels (tAKT) and phosphorylated AKTs129 protein   were elevated in tumor samples compared to para-
            (pAKT) were significantly elevated in LUAD and LUSC   neoplastic tissues (Figure S9A and B). Almost all tumor
            samples compared to para-neoplastic tissues, with the   specimens (95%) showed positive-to-strong positive
            highest levels observed in LUSC (Figure  6C). Notably,   pNPM1 staining, with an R>2 over para-neoplastic tissues
            pAKT levels did not correlate with CK2 subunit levels in   (para-LUAD = 45%; para-LUSC =  44%) (Figure S9B).
            either LUAD or LUSC specimens (Figure  6D). Finally,   Interestingly, pNPM1 phosphorylation levels correlated
            CSNK2A1 and CSNK2A2 showed strong correlations with   with CSNK2A2, but not with CSNK2A1 in LUAD; in
            each other in both LUAD (R = 0.504) and LUSC (R = 0.661)   contrast, in LUSC, pNPM1 levels correlated with both
            samples, whereas CSNK2B positively correlated only with   catalytic subunits, CSNK2A1 and CSNK2A2 (Figure S9C;
            CSNK2A1 in LUAD (R = 0.398) (Figure 6D; Table S5).  Table S6). Finally, CK2 catalytic subunits showed strong


            Volume 3 Issue 4 (2024)                         7                                 doi: 10.36922/td.4571
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