Fig. 1: Global methylation patterns of primary tumors and clinical associations. | Communications Biology

Fig. 1: Global methylation patterns of primary tumors and clinical associations.

From: Genome-wide DNA methylation patterns reveal clinically relevant predictive and prognostic subtypes in human osteosarcoma

Fig. 1: Global methylation patterns of primary tumors and clinical associations.The alt text for this image may have been generated using AI.

a Manhattan plot of genome-wide variance in methylation. The 5% most variantly methylated sites, those above the red line, are analyzed as the Global profile. b Unsupervised hierarchical clustering of the TARGET samples using the Global profile. Cluster reproducibility (R) indices were high, 0.98/0.95 for two and three groups respectively. c Supervised β value heatmap of the 1725 CpG sites differentially methylated (FDR < 0.1) between the very poor prognosis (ii) and other cluster groups (i and iii) in (b). d Supervised heatmap of the Global profile. Samples are ordered from low to high average β value. Two sample groups generated by a median split of the average β values were significantly associated with pathologic response to chemotherapy (Fisher’s exact p = 0.002, OR = 10.2, 95% CI: 2.5–41.7). e MetDx stratified RFS analysis of the two primary Global cluster groups (not metastatic: median RFS = 63.5 (i) and 104.7 mo. (iii), metastatic: median RFS = 2.3 (i) and 26.7 mo. (iii), pooled Log-Rank p = 0.006). f RFS analysis of the three primary cluster groups (median RFS = 11.5 (ii), 26.7 (i), and 104.7 mo. (iii), Log-Rank p = 5.0 × 10−4). Pairwise RFS analysis of the three primary cluster groups. Short (ii, 11.5 mo.) vs. intermediate (i, 26.7 mo.) median RFS Log-Rank p = 0.034. Intermediate (i) vs. long (iii, 104.7 mo.) median RFS Log-Rank p = 0.022. Short (ii) vs. long (iii) median RFS Log-Rank p = 2.7 × 10−5. g MetDx stratified RFS analysis of the low and high average methylation groups (median split) from c (not metastatic: median RFS = 65.5 and 104.7 mo., metastatic: median RFS = 3.5 and 16.9 mo., pooled Log-Rank p = 0.044). h MetDx stratified OS analysis of the two primary cluster groups (not metastatic: median OS = NYR (i) and NYR (iii), metastatic: median OS = 20.6 (i) and 111.9 mo. (iii), pooled Log-Rank p = 5 × 10−4). i OS analysis of the three primary cluster groups (median OS = 20.4 (ii), 94,7 mo. (i), and NYR (iii), Log-Rank p = 7.4 × 10−4. Pairwise OS analysis of the three primary cluster groups. Short (ii, 20.4 mo.) vs. intermediate (i, 94.7 mo.) median OS Log-Rank p = 0.067. Intermediate (i) vs. long (iii, NYR) median OS Log-Rank p = 0.008. Short (ii) vs. long (iii) median OS Log-Rank p = 1.8 × 10−4. j MetDx stratified OS analysis of the low and high average methylation groups (median split) from (c) (not metastatic: median OS = 126.6 mo. and NYR, metastatic: median OS = 9.7 and 28.2 mo., pooled Log-Rank p = 0.076).

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