A novel risk stratification model based on the Children's Hepatic Tumours International Collaboration-Hepatoblastoma Stratification and deoxyribonucleic acid methylation analysis for hepatoblastoma

Kondo, Takafumi; Honda, Shohei; Suzuki, Hiromu; Ito, Yoichi M.; Kawakita, Issei; Okumura, Kazuyoshi; Ara, Momoko; Minato, Masashi; Kitagawa, Norihiko; Tanaka, Yukichi; Tanaka, Mio; Shinkai, Masato; Hishiki, Tomoro; Watanabe, Kenichiro; Ida, Kohmei; Takatori, Atsushi; Hiyama, Eiso; Taketomi, Akinobu

A novel risk stratification model based on the Children's Hepatic Tumours International Collaboration-Hepatoblastoma Stratification and deoxyribonucleic acid methylation analysis for hepatoblastoma

Kondo, Takafumi; Honda, Shohei; Suzuki, Hiromu et al.

European journal of cancer, 2022, 172, 311-322

Permalink : https://hdl.handle.net/2115/90361

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/90361
タイトル	A novel risk stratification model based on the Children's Hepatic Tumours International Collaboration-Hepatoblastoma Stratification and deoxyribonucleic acid methylation analysis for hepatoblastoma
著者	Kondo, Takafumi ; Honda, Shohei ; Suzuki, Hiromu ; Ito, Yoichi M. ; Kawakita, Issei ; Okumura, Kazuyoshi ; Ara, Momoko ; Minato, Masashi ; Kitagawa, Norihiko ; Tanaka, Yukichi ; Tanaka, Mio ; Shinkai, Masato ; Hishiki, Tomoro ; Watanabe, Kenichiro ; Ida, Kohmei ; Takatori, Atsushi ; Hiyama, Eiso ; Taketomi, Akinobu
著者名 Kondo, Takafumi
e-Rad_Researcher 90588089 著者名 Honda, Shohei
著者名 Suzuki, Hiromu
e-Rad_Researcher 10334236 著者名 Ito, Yoichi M.
著者名 Kawakita, Issei
著者名 Okumura, Kazuyoshi
e-Rad_Researcher 30741219 著者名 Ara, Momoko
著者名 Minato, Masashi
著者名 Kitagawa, Norihiko
著者名 Tanaka, Yukichi
著者名 Tanaka, Mio
著者名 Shinkai, Masato
著者名 Hishiki, Tomoro
著者名 Watanabe, Kenichiro
著者名 Ida, Kohmei
著者名 Takatori, Atsushi
著者名 Hiyama, Eiso
e-Rad_Researcher 70363364 著者名 Taketomi, Akinobu
言語	英語
キーワード	Hepatoblastoma
	CHIC
	DNA methylation
	Biomarker
	Risk stratification
発行日	2022-09
出版者	Elsevier
収録物名	European journal of cancer
巻(号)	172
ページ	311-322
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
権利情報	Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報	© 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/
PISSN	0959-8049
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1016/j.ejca.2022.06.013