| Title: | A novel risk stratification model based on the Children's Hepatic Tumours International Collaboration-Hepatoblastoma Stratification and deoxyribonucleic acid methylation analysis for hepatoblastoma |
| Authors: | Kondo, Takafumi Browse this author |
| Honda, Shohei Browse this author →KAKEN DB |
| Suzuki, Hiromu Browse this author |
| Ito, Yoichi M. Browse this author →KAKEN DB |
| Kawakita, Issei Browse this author |
| Okumura, Kazuyoshi Browse this author |
| Ara, Momoko Browse this author →KAKEN DB |
| Minato, Masashi Browse this author |
| Kitagawa, Norihiko Browse this author |
| Tanaka, Yukichi Browse this author |
| Tanaka, Mio Browse this author |
| Shinkai, Masato Browse this author |
| Hishiki, Tomoro Browse this author |
| Watanabe, Kenichiro Browse this author |
| Ida, Kohmei Browse this author |
| Takatori, Atsushi Browse this author |
| Hiyama, Eiso Browse this author |
| Taketomi, Akinobu Browse this author →KAKEN DB |
| Keywords: | Hepatoblastoma |
| CHIC |
| DNA methylation |
| Biomarker |
| Risk stratification |
| Issue Date: | Sep-2022 |
| Publisher: | Elsevier |
| Journal Title: | European journal of cancer |
| Volume: | 172 |
| Start Page: | 311 |
| End Page: | 322 |
| Publisher DOI: | 10.1016/j.ejca.2022.06.013 |
| Abstract: | Introduction: Hepatoblastoma (HB) is the most common paediatric liver tumour, and epigenetic aberrations may be important in HB development. Recently, the Children's He-patic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) devel-oped risk stratification based on clinicopathological factors. This study aimed to construct a more accurate model by integrating CHIC-HS with molecular factors based on DNA methylation. Methods: HB tumour specimens (N = 132) from patients treated with the Japanese Pediatric Liver Tumors Group-2 protocol were collected and subjected to methylation analysis by bisul-fite pyrosequencing. Associations between methylation status and clinicopathological factors, overall survival (OS), and event-free survival (EFS) were retrospectively analysed. We inves-tigated the effectiveness of the evaluation of methylation status in each CHIC-HS risk group and generated a new risk stratification model. Results: Most specimens (82%) were from post-chemotherapy tissue. Hypermethylation in > 2 of the four genes (RASSF1A, PARP6, OCIAD2, and MST1R) was significantly associated with poorer OS and EFS. Multivariate analysis indicated that > 2 methylated genes was an in-dependent prognostic factor (hazard ratios of 6.014 and 3.684 for OS and EFS, respectively). Two or more methylated genes was also associated with poorer OS in the CHIC-very low (VL)-/low (L)-risk and CHIC-intermediate (I) risk groups (3-year OS rates were 83% vs. 98% and 50% vs. 95%, respectively). The 3-year OS rates of the VL/L, I, and high-risk groups in the new stratification model were 98%, 90%, and 62% (vs. CHIC-HS [96%, 82%, and 65%, respectively]), optimising CHIC-HS. Conclusions: Our proposed stratification system considers individual risk in HB and may improve patient clinical management. (C) 2022 Elsevier Ltd. All rights reserved. |
| Rights: | © 2022. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/90361 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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