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Fig. 5 | Clinical Epigenetics

Fig. 5

From: The signature of liver cancer in immune cells DNA methylation

Fig. 5

Progressive hypomethylation of PD-1 gene during HCC progression. a Correlation (linear fit) between average beta values for cg14453145 positioned at the TSS region of PD-1 and control (CTRL) (stage code 0), hepatitis B (HepB) (1), hepatitis C (HepC) (2), and the four stages of HCC (St_1 to St_4) (3–6) diagnoses (equation and R values are indicated). One way ANOVA showed a highly significant effect of diagnosis on DNA methylation (p = 1 × 10−13; F = 20.77). Bonferroni adjusted pairwise comparison revealed significant differences between HCC stage 1 and control (p = 0.0058) and hepatitis B (p = 0.00079); between stage 2 and control (p = 0.0004) and hepatitis B (p = 4.9 × 10–5); between stage 3 and control (p = 4.8 × 10–9), hepatitis B (p = 4.9 × 10–10), hepatitis C (p = 1.8 × 10–5) and stage 1(p = 0.00993); between stage 4 and control (p = 2.1 × 10–8), hepatitis B (p = 2.3 × 10−9), hepatitis C (p = 5.9 × 10−5) and stage1 (p = 0.00558). b Correlation (linear fit) between average beta values of 24 CGs associated to the PD-1 gene on the Illumina 450k arrays that were hypomethylated in HCC (average methylation score was calculated per person, the average of these scores were then calculated per group). There was a highly significant effect of diagnosis on DNA methylation as determined by one way ANOVA (p = 2.2 × 10–16, F = 52.74). Bonferroni adjusted pairwise comparison revealed significant differences between stage 1 HCC and control (p = 1.2 × 10−7), hepatitis B (p = 7 × 10−8), hepatitis C (p = 0.00487), stage 3 (p = 0.00081), and Stage 4 (p = 6.4 × 10−6); between stage 2 and control (p = 4.7 × 10−11), hepatitis B (p = 2.8 × 10−11), hepatitis C (p = 3.8 × 10−6), and stage 4 (p = 0.00645); between stage3 and control (p = 3.4 × 10−15), hepatitis B (2.1 × 10−15), hepatitis C (2.1 × 10−10), and stage 1 (p = 0.00081); and between stage 4 and control (2 × 10−16), hepatitis B (2 × 10−16), hepatitis C (1.8 × 10−12), stage 1 (6.4 × 10−6), and Stage 2 (p = 0.00645). c Heat map presentation of hierarchical clustering (city block) of 69 people by 5’DMR whose average methylation correlates with HCC progression

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