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. 2021 Sep 20;12:5423. doi: 10.1038/s41467-021-25430-9

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 7 — a, b Samples were stratified according to the clinical parameters a and molecular-defined subtypes b. a Age, age at diagnosis; PRETEXT, the PRETEXT staging system; Annotation factors (M distant metastasis, + positive for VPERFNH, − negative for the annotation factors); Histology histologic subtypes. b Expression, gene expression; CIN, chromosomal instability; Enhancer, enhancer methylation; Promoter, promoter methylation. Statistical significance was analyzed using the log-rank test. c Surrogate methylation marker DLX6-AS1 (cg22421859, chr7:96622043) for all childhood hepatoblastoma (HB) cases (left) and limited subgroup (middle, for infant HB; right, for AF-positive cases). d Volcano plots of differential methylation between older HB cases (P1, P2) and younger cases (P3, P4). The heat map in the bottom shows the methylation status of the 10 most significant CpG sites using the two-sided Fisher’s exact test. e Surrogate methylation, DLX6-AS1 to distinguish methylation subtypes. Statistical significance was analyzed using Fisher’s exact test. f Sankey diagram stratifying the HB cases with poor prognosis by DLX6-AS1 methylation.