FIGURE SUMMARY
Title

DEHP-Induced Glioblastoma in Zebrafish Is Associated with Circadian Dysregulation of PER3

Authors
Men, S., Xu, J., Yang, Z., Yan, Z.
Source
Full text @ Toxics

PER3 expression is significantly downregulated in several cancers, including GBM. (A) TCGA database analysis showed the expression levels of PER3 in 33 cancer tissues and their corresponding surrounding normal tissues. * p < 0.05; ** p < 0.01; *** p < 0.001. (BD) The expression levels of PER3 in cases (B) GSE29458, (C) GSE22866, and (D) GSE14805 in GBM tissues had significantly higher expression levels than normal brain tissues. (E,F) The 706 GBM patients in the TCGA-GBMLGG database were categorized into high-expression and low-expression groups based on the median PER3 expression level. (E) Volcano plot and (F) heat map demonstrating the expression levels of specific mRNAs in GBM patients.

PER3 expression is significantly downregulated in several cancers, including GBM. (A) TCGA database analysis showed the expression levels of PER3 in 33 cancer tissues and their corresponding surrounding normal tissues. * p < 0.05; ** p < 0.01; *** p < 0.001. (BD) The expression levels of PER3 in cases (B) GSE29458, (C) GSE22866, and (D) GSE14805 in GBM tissues had significantly higher expression levels than normal brain tissues. (E,F) The 706 GBM patients in the TCGA-GBMLGG database were categorized into high-expression and low-expression groups based on the median PER3 expression level. (E) Volcano plot and (F) heat map demonstrating the expression levels of specific mRNAs in GBM patients.

Functional enrichment analysis of differentially expressed genes in GBM based on PER3 expression levels. (A) GO functional enrichment analysis of PER3-associated differential genes showing enrichment for biological process (BP), cellular component (CC), and molecular function (MF). (BM) GSEA genomic enrichment analysis of altered signaling pathways in GBM tissues based on PER3-related differential genes in GBM high and low expression groups.

Correlation analysis of immune cell infiltration with PER3 expression in GBM. (A) Spearman’s correlation analysis of the infiltration level of 24 immune cells with the expression level of PER3 in GBM tissues. (BI) Infiltration levels of (B) central memory cells, (C) γδ T cells, (D) effector memory T cells, (E) follicular helper T cells, (F) neutrophils, (G) macrophages, (H) type 2 helper T cells, and (I) CD56dim NK cells in the high and low expression groups. ns, p ≥ 0.05; * p < 0.05; *** p < 0.001.

Correlation analysis of PER3 expression level with oncogene (A) TP53, (B) CPEB3, (C) CASP3, and immune checkpoint (D) CD276, (E) HLA-A, and (F) TNFRSF4 expression level in glioblastoma tissues.

DNA methylation level of PER3 gene is associated with prognosis of GBM.

PER3 expression levels correlate with a variety of clinical case characteristics in GBM patients. (AI) The correlation analysis between PER3 expression level and (A) WHO grade, (B) Primary therapy outcome, (C) Age, (D) DSS, (E) OS, (F) PEI, (G) 1p/19q codeletion, (H) IDH status, (I) Histological type. ns, p ≥ 0.05; * p < 0.05; *** p < 0.001.

PER3 expression levels correlate with a variety of clinical case characteristics in GBM patients. (AI) The correlation analysis between PER3 expression level and (A) WHO grade, (B) Primary therapy outcome, (C) Age, (D) DSS, (E) OS, (F) PEI, (G) 1p/19q codeletion, (H) IDH status, (I) Histological type. ns, p ≥ 0.05; * p < 0.05; *** p < 0.001.

PER3 exhibits high prognostic predictive value in patients with GBM. k-M plots show the differences in (A) overall survival, (B) disease-specific survival, and (C) progression-free intervals in patients with GBM in the high and low PER3 expression groups. p < 0.05 was statistically significant.

PER3 exhibits excellent diagnostic and prognostic performance in GBM (A) three-factor diagnostic ROC curve. (B) Time-dependent ROC curves predicting 1-, 5-, and 7-year survival rates in glioblastoma patients based on PER3 expression levels.

Toxic effects of DEHP on zebrafish. (A) Effects of DEHP exposure on the differential expression of PER3 gene in the zebrafish brain. * p < 0.05. (B) Effects of DEHP exposure on zebrafish growth and development. (C) Effects of zebrafish exposure on spontaneous locomotion of juvenile fish. (D) Behavioral effects of light and dark cyclic stimulation on different subgroups of zebrafish. (E) Analysis of the homology of zebrafish and human PER3 protein.

Acknowledgments
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