| Project/Area Number |
20K07391
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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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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Kobe University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
松岡 宏 藤田医科大学, 医学部, 教授 (40367719)
大崎 博之 神戸大学, 保健学研究科, 准教授 (80438291)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2022: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 食道癌 / 術前薬物療法 / 効果予測 / SLCトランスポーター / p53 / 免疫組織化学染色 / PD-L1 |
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| Outline of Research at the Start |
本研究では、有効な分子標的薬が見出されていない食道癌薬物療法の個別化を実現させるために、シスプラチンと5-FUの併用による術前薬物療法が施行されたIB/II/III期食道癌の病理組織標本を対象として、SLCトランスポーターの発現と薬物療法の組織学的効果、無再発生存期間及び全生存期間との関連性を明らかにする。それによって、SLCトランスポーターの免疫組織化学染色による食道癌薬物療法個別化の可能性を証明する。
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| Outline of Final Research Achievements |
We assessed the predictive value of immunostaining of organic cation transporter 1 (OCT1) and p53 for the effect of preoperative chemotherapy with cisplatin/5-FU (CF) or docetaxel/CF in esophageal cancer. Mutant-type expression of p53 (p53MT-ex) in pretreatment biopsies was significantly correlated with poor histopathological response. In combined analysis, tumors with either p53MT-ex or low expression of OCT1 (OCT1Low) showed a significant correlation with poor response compared with tumors with the opposite pattern. Combined p53/OCT1 was the only independent predictor of histopathological response. When stratified by chemotherapy regimen, combined p53/OCT1 was a significant predictor of response in the CF group in univariate and multivariate analyses. These results suggest that either p53MT-ex or OCT1Low expression may be a potential predictor of poor response to preoperative chemotherapy with the CF regimen in esophageal cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
術前薬物療法を施行した進行食道癌患者の治療前生検材料を対象として、薬物療法の効果予測因子の発現を明らかにすることは、進行食道癌の治療戦略の構築、薬物療法の個別化を実現する手掛かりとなる可能性がある。
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