Epigenetic analyses to establish a molecular-genetic marker for treatment outcome in hepatoblastomas

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10915
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatric surgery
• Research Institution: Hokkaido University
• Principal Investigator: Honda Shohei 北海道大学, 大学病院, 助教 (90588089)
• Co-Investigator(Kenkyū-buntansha): 北河 徳彦 地方独立行政法人神奈川県立病院機構神奈川県立こども医療センター(臨床研究所), 臨床研究所, 医長 (00585135) ; 田中 祐吉 地方独立行政法人神奈川県立病院機構神奈川県立こども医療センター(臨床研究所), 臨床研究所, 臨床研究所長 (50420691) ; 武冨 紹信 北海道大学, 医学研究院, 教授 (70363364) ; 宮城 久之 北海道大学, 医学研究院, 特任助教 (50596442)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 肝芽腫 / ＤＮＡメチル化 / エピゲノム異常 / 予後予測マーカー

Outline of Final Research Achievements

We first performed genome-wide methylation profiling in a total of 11 samples. We identified 15,102 probes which were significantly hypermethylated in chemo-resistant group. We next obtained resistant HuH6 cells by repeated cisplatin (CDDP) treatments and detected 119 genes which were significantly downregulated in the resistant cells. Using Venn diagram, we selected 5 candidate methylated genes associated with chemoresistance. Therefore, we next performed methylation analysis of the 5 selected genes in 55 HB tumor specimens. Event free survival curves classified by the methylation status and Kaplan-Meier analysis showed that tumors in which three genes were methylated were significantly associated with poorer prognosis. We expect that these biomarkers may be used to stratify the hepatoblastoma patients efficiently, and develop better therapeutic strategies.

Free Research Field

小児外科