| Project/Area Number |
17K09614
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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 |
Respiratory organ internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
西村 善博 神戸大学, 医学部附属病院, 教授 (20291453)
立原 素子 神戸大学, 医学研究科, 講師 (40448626)
田村 大介 神戸大学, 医学研究科, 医学研究員 (80646597)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
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: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 非小細胞肺がん / CARD9 / 肺腺癌 / 免疫染色 / 微小乳頭状構造 / スパイラルアレイ / オルガノイド培養 / 肺がん / 三次元培養 / 癌 |
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| Outline of Final Research Achievements |
A spiral array block was created using paraffin-embedded blocks from 74 patients. First, immunostaining was focused on Caspase recruitment domain-containing protein 9 (CARD9), which is highly expressed in bone marrow cells and plays a central role in innate immunity. High-level CARD9 expression was found in 32.4% of all lung adenocarcinomas, with a significantly worse prognosis than low expression (P = 0.0402). Moreover, univariate analysis and multivariate analysis revealed that high expression of CARD9 was an independent poor prognostic factor for lung adenocarcinoma.The expression of CARD9 in lung adenocarcinoma cell lines such as A549, PC9 and II18 was knocked down with siRNA. It was found that knocked down of CARD9 diminished growth potential and increased apoptotic cells. Furthermore, when NFκB activation was evaluated by Western blotting, it was found that knockdown of CARD9 suppressed NFκB activation.
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| Academic Significance and Societal Importance of the Research Achievements |
現在までに、非小細胞肺がん（NSCLC）の予後予測因子として、特定の臨床因子やTNM分類、病期などが確立されている。しかしながら、NSCLCの予後は、同じ病期の腫瘍を持つ患者の間でも大きく異なることがあり、実際、ステージIの患者の20%は手術後に再発を経験している。したがって、ステージIの患者に対するアジュバント治療の必要性が一部の患者にある可能性がある。CARD9は肺腺がんの新しい予後不良因子として、術後化学療法の適切な患者選択に活用されるのみならず、肺腺がんの新しい分子標的となりうる可能性がある。
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