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Fig. 6 | Breast Cancer Research

Fig. 6

From: Epigenetic silencing of CREB3L1 by DNA methylation is associated with high-grade metastatic breast cancers with poor prognosis and is prevalent in triple negative breast cancers

Fig. 6

CREB3L1 mRNA expression and DNA methylation from human breast tumor samples in The Cancer Genome Atlas (TCGA) database. a, b CREB3L1 mRNA expression varies for different tumor stages (a: n = normal (70 samples); numbers of samples for each stage I to X: 80, 287, 139, 5, 4) and subtypes (b: numbers of samples: 70, 263, 15, 76) of breast tumors. Statistical differences were analyzed using post-hoc pairwise comparison: *p <0.05; ***p <0.001. c Using cBioPortal containing TCGA data from 737 breast cancer cases, there is an inverse relationship between CREB3L1 mRNA expression and CREB3L1 gene methylation that is very significant (Spearman correlation, r = −0.464, p <0.001). d Focusing on samples where the tumor subtype was known, the lowest CREB3L1 mRNA expression and also the highest CREB3L1 gene methylation was found most often in triple negative breast cancer (TNBC) (p <0.0001). e Data within TCGA contained an analysis of 26 regions (50 nucleotides each) within the CREB3L1 gene that had been analyzed for DNA methylation (Additional file 8: Table S4). Of these, 20 showed methylation changes between normal (97 samples) and breast tumors (764 samples), as shown (heat map): red high methylation, white mean methylation, blue low methylation. Methylation regions are numbered (bottom (1–20)) with the sequences listed in Additional file 8: Table S4, and their approximate locations are shown (f). f Schematic of CREB3L1 gene organization. The 5′ and 3′ untranslated regions (black boxes), exons (gray boxes with numbers above) and CpG islands (hatched boxes) are shown. The first CpG island is 672 nucleotides long between −119 and 554, relative to the translational start site, and contains 51 CpG sites. The second CpG island is 610 nucleotides long between 17154 and 17822 within intron 1 and contains 56 CpG sites. The approximate locations of 20 cg probes for methylation are indicated underneath and numbered as in e

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