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Fig. 6 | Clinical Epigenetics

Fig. 6

From: Combined inhibition of histone deacetylase and cytidine deaminase improves epigenetic potency of decitabine in colorectal adenocarcinomas

Fig. 6

Kaplan–Meier survival plots of drug-responsive genes for 270 COAD patients. Genes either up- or downregulated in colon cancer cells following drug treatment were assessed for their prognostic value in COAD patients. A1 Shown are Kaplan–Meier survival curves for individual DEGs and the combined genes signature. High expression of decitabine-regulated genes is associated with better survival. The HR ranges between 0.5 and 0.6 and is statistically significant. A2 Shown are Kaplan–Meier survival curves for individual DEGs and the combined genes signature. High expression of PBA-regulated genes is associated with better survival. The HR ranges between 0.5 and 0.6 and is statistically significant. A3 Shown are Kaplan–Meier survival curves for individual DEGs. High expression of decitabine-/PBA-regulated genes is associated with better survival. The HR is 0.6 and statistically significant. B1 Shown are Kaplan–Meier survival curves for individual DEGs repressed by decitabine treatment and the combined gene signature. Lower expression of decitabine-repressed genes is associated with better outcome. The HR ranges between 1.5 and 2 and is statistically significant. B2 Shown are Kaplan–Meier survival curves for 2 genes repressed by PBA treatment. Lower expression of PBA-repressed genes is associated with better survival. The HR ranges between 1.7 and 1.8 and is statistically significant. B3 Shown are Kaplan–Meier survival curves for 5 individual DEGs repressed by the combined decitabine/PBA treatment and the combined gene signature. Lower expression of the genes is associated with better survival. For individual genes, the HR ranges between 1.7 and 1.9 and for the combined gene signature is 2.3. C1 Shown are Kaplan–Meier survival curves for hsa-miR-1249 and hsa-miR-375. High expression of these tumor-suppressor miRNAs is associated with better survival. The HR ranges between 0.56 and 0.6 and is statistically significant. C2 Shown are Kaplan–Meier survival curves for has-miR-129-2 and has-miR-193a. Lower expression of these oncomirs is associated with better survival. The HR ranges between 1.66 and 1.7 and is statistically significant. D Venn diagram of hsa-miR-129-2 validated and decitabine-regulated genes. We queried the miRNet database to search for validated hsa-miR-129-2 target genes and compared the gene targets with decitabine regulated genes. Subsequently, we considered their prognostic value among 270 COAD patients (panel A1). The Venn diagram shows the number of unique and common regulated gene targets of hsa-miR-129-2 and decitabine following drug treatment of colon cancer cells for 96 h. High expression of the four common regulated genes is associated with better survival in COAD patients. Decitabine treatment repressed the expression of hsa-miR-129-2, and this resulted in induced expression of four hsa-miR-129-2 target genes. Decitabine treatment caused upregulation of NOX1 independent of hsa-miR-129-2

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