| Project/Area Number |
17K10469
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Fukushima Medical University (2019)
Gunma University (2017-2018) |
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Principal Investigator |
YOSHIMOTO YUYA 福島県立医科大学, 医学部, 講師 (80594390)
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| Co-Investigator(Kenkyū-buntansha) |
野田 真永 埼玉医科大学, 医学部, 教授 (60396645)
村田 和俊 群馬大学, 重粒子線医学推進機構, 助教 (60644557)
佐藤 浩央 群馬大学, 重粒子線医学推進機構, 助教 (90750571)
尾池 貴洋 群馬大学, 医学部附属病院, 講師 (10643471)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 子宮頸癌 / 抗腫瘍免疫 / 放射線治療 / 分子標的薬 / precision medicine / 変異解析 / 腫瘍浸潤T細胞 / 腫瘍免疫 / 放射線腫瘍学 / 腫瘍免疫学 |
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| Outline of Final Research Achievements |
[Objective] To elucidate tumoral mutation profiles and immune profilies associated with outcome in uterine cervical cancer (UCC) patients treated with definitive radiotherapy.
[Methods] Newly diagnosed and pathologically confirmed treated with definitive radiotherapy were analyzed. DNA was extracted from pre-treatment tumor biopsy specimens and exons of 409 cancer-related genes were sequenced using a next-generation sequencer. Immunohistochemical studies were also performed and analyzed for correlation with clinical outcome.
[Results & Conclusions] The presence of CD8+TILs, CD3+TILs in the tumor nests has the potential to be an independent favorable prognostic factor for UCC patients treated with definitive radiotherapy. Also, the prevalence of mutation in FGFR family genes (i.e., FGFR1–4) was as high as that for PIK3CA and the FGFR mutation was associated with worse PFS. These results warrant validation by further prospective study.
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| Academic Significance and Societal Importance of the Research Achievements |
子宮頸癌放射線治療においても抗腫瘍免疫が予後に関与することを明らかにした。一方、日本人コホートを対象とした子宮頸癌の網羅的遺伝子変異解析を初めて行い、PIK3CAやFBXW7、ARID1Aの変異が高頻度に認められた。このことは、癌ゲノム解析による個別化医療時代における重要な参照情報となる。さらに、FGFRなどレセプターキナーゼ遺伝子の変異を有する症例では、治療反応性、予後共に不良であることを新規に見出した。子宮頸癌は抗がん剤に対する奏効率が低く、一方で、レセプターキナーゼ遺伝子に対する分子標的薬剤は既に他がんで臨床応用されているために、医師主導治験などでで速やかに臨床導入出来る可能性がある。
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