Methylation analyses related to CDDP-resistant hepatoblastoma
| Project/Area Number |
18K16250
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Hokkaido University |
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Principal Investigator |
Ara Momoko 北海道大学, 大学病院, 医員 (30741219)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肝芽腫 / メチル化 / シスプラチン耐性 / DNAメチル化異常 / 遺伝子発現異常 / DNAメチル化 / 遺伝子発現変動 / 薬剤耐性 |
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| Outline of Final Research Achievements |
Aberrant DNA methylation is a major regulatory mechanism in carcinogenesis, progression and malignant transformation of hepatoblastoma. This is also assumed to be involved in cisplatin (CDDP) resistance with poor prognosis, and this study analyzed epigenomic aberrations involved in CDDP resistance in hepatoblastoma in order to establish molecular markers and new therapeutic targets. Based on the results of methylation bead array and microarray analyses, CSF3R was selected as one of the key genes associated with CDDP resistance. We analyzed the CSF3R methylation rate using bisulfite pyrosequencing in 38 preoperative CDDP-sensitive tumors, and the hypermethylation group showed a significantly higher recurrence rate than the low methylation group.
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| Academic Significance and Societal Importance of the Research Achievements |
肝芽腫にとって最も重要な抗がん剤であるシスプラチン(CDDP)に対する耐性機序にエピゲノム異常が関わっていると想定し、その候補遺伝子の1つとしてCSF3Rを同定した。CSF3Rの高メチル化は肝芽腫の予後と相関し、予後予測因子として有用である。本研究においてその他の直接的なCDDP耐性に寄与する新たな遺伝子の探索には至らなかったが、エピゲノム処理を施した細胞株実験から一部の癌遺伝子の発現変化がみられており、今後肝芽腫に対してエピゲノム異常を治療ターゲットとする新たな取り組みにつながる可能性が示唆された。
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Report
(6 results)
Research Products
(7 results)
