| Project/Area Number |
17K16580
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Digestive surgery
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| Research Institution | Juntendo University |
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Principal Investigator |
Okazawa Yu 順天堂大学, 医学部, 助教 (10794604)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 大腸癌 / DNAメチル化 / イリノテカン / 抗癌剤感受性 / HDRA / タキサン / CHFR / リキッドバイオプシー |
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| Outline of Final Research Achievements |
Primary tumor in colorectal cancer patients were investigated. (1) We investigated the correlation between DNA methylation level and inhibition rate by irinotecan (SN-38) using the Histoculture drug response assay (HDRA) method. (2) The correlation between responses to treatment and DNA methylation of the CHFR gene in patients (n=47) where irinotecan-based systemic chemotherapy was performed for advanced/recurrent colorectal cancer was examined.(1) When CHFR-RMV in primary cancer tissue was divided into two groups, i.e., the high group (n=28) and the low group (n=18), significant difference was recognized in the inhibition rate by irinotecan (SN-38) using the HDRA method between the two groups. (2) Progression-free survival from the initiation of irinotecan-based systemic chemotherapy was significantly better in the high CHFR-RMV group (p=0.04).
Our current study suggests that CHFR-RMV in primary cancer tissue is a predictor of response in irinotecan-based systemic chemotherapy.
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| Academic Significance and Societal Importance of the Research Achievements |
DNAメチル化は多くの癌腫において癌の発生や進展に重要な役割を果たしていることが報告され，これまでにも早期発見や術後再発予測，治療効果のモニタリングにおける有用性について検討がなされてきている．近年，CHFR遺伝子のDNAメチル化が予後予測やirinotecanを用いた全身化学療法の効果予測に有用であると報告されている．今回われわれは，大腸癌原発巣におけるCHFR遺伝子のDNAメチル化がirinotecanベースの全身化学療法の効果予測因子になりうるかについて検討した．
本検討結果により，CHFR-RMVはirinotecanベースの全身化学療法における効果予測因子であることが示唆された．
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