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Gene & Protein in Disease                                             Pediatric glioma circadian clock genes




            A                                      B









                                                         D


            C













            Figure 5. Comparison of the limited clock gene set expression in four medulloblastoma subtypes. (A) Cluster analysis from scRNA-seq data, as reported by
            Riemondy et al.,  shows Group 4 (G4), Group 3 (G3), WNT, and SHH subtypes in cells pooled from patient tumor samples and separated from immune
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            cells and other non-malignant cells. (B) Average normalized expression of the core clock gene set in the MB subtypes. Results are from cells with detected
            gene expression. (C) Clock gene expression is significantly higher in the G3 and G4 subtypes than in WNT and SSH (*p<0.05, **p<0.01). (D) All core clock
            genes are expressed in the cells identified as immune cells. The percentage of cells expressing the clock genes is lowest in the immune cells, except for PER1.
            Results and cluster plots were accessed through UCSC Cell Viewer.


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            Table 5. Age‑dependent differential circadian clock gene   from de Bont et al.  was also examined, and there were
            expression in primary SHH‑MB                       no significant differences between recurrent and original
                                                               tumors, although in this dataset, GlioVis grouped results
            Gene symbol     Adjusted P value  Log fold change  from multiple pediatric tumor types in the analysis, thereby
            CRY2               0.00152          −0.6151        possibly masking significant differences. Furthermore, the
            HLF                0.00618           −1.278        Witt and Schwartzentruber datasets included some adult
            NR1D1              0.00277          −0.7031        patient samples.
            NR1D2              0.00436           −1.332
            PER3               0.00106           −1.258        4. Discussion
            RORA               0.00151          −0.5289        4.1. Consistent clock gene expression patterns
            Note: Patients under 10 years of age versus 10 years and above. From   observed in adult and pediatric gliomas
            Kool et al.  and GEO.
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                                                               More clock genes were significantly repressed than
                                                               overexpressed in the pediatric and adult gliomas relative
            in Gliovis. Very few differences were observed when   to normal tissue, which is consistent with evidence that
            testing with Tukey’s HSD, and these were not consistent   clock genes are generally downregulated in cancers,
            between ependymoma datasets or when  they  were    perhaps through epigenetic modification. 59-62  Although
            compared with the GBM results. The Hoffman dataset   this reduced expression might impair the functioning of
            showed lower ARNTL and elevated DBP expression in the   the circadian clock mechanism, GSCs of adult gliomas and
            recurrent tumors (p<0.05). The Witt dataset showed lower   cells of several other cancers are rhythmic and appear to
            CRY2 (p<0.01) and lower DBP, HLF, and PER3 expression   depend on their own circadian clock for survival. 9,10,13,14,63-68
            (p<0.05) in the recurrent group. The Schwartzentruber   Therefore, GSCs in pediatric tumors might remain
            dataset showed higher expression of ARNTL2 and PER2 in   rhythmic independent of whether the rest of the tumor
            recurrent tumors (p<0.01). Datasets were also compared   mass  generates  a circadian rhythm. When  considering
            in terms of patient gender, and no significant differences   the role of circadian genes in any cancer, it is important to
            were detected in any of these datasets. Finally, the dataset   consider how they could be acting through the circadian


            Volume 4 Issue 2 (2025)                         13                               doi: 10.36922/gpd.4112
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