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Comprehensive analysis of circulating microRNAs as predictive biomarkers for sorafenib therapy outcome in hepatocellular carcinoma
https://kagawa-u.repo.nii.ac.jp/records/152
https://kagawa-u.repo.nii.ac.jp/records/152a195a7cc-4d73-49ee-b15f-43115be46489
| 名前 / ファイル | ライセンス | アクション |
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本文 (769.3 kB)
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内容の要旨 (81.3 kB)
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審査の結果の要旨 (384.7 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||||||
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| 公開日 | 2020-07-10 | |||||||||||||
| タイトル | ||||||||||||||
| タイトル | Comprehensive analysis of circulating microRNAs as predictive biomarkers for sorafenib therapy outcome in hepatocellular carcinoma | |||||||||||||
| 言語 | en | |||||||||||||
| 言語 | ||||||||||||||
| 言語 | eng | |||||||||||||
| 資源タイプ | ||||||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||||||
| 資源タイプ | doctoral thesis | |||||||||||||
| その他（別言語等）のタイトル | ||||||||||||||
| その他のタイトル | 肝細胞癌に対するソラフェニブ治療における予測バイオマーカーとしての血清circulating microRNAの網羅的解析 | |||||||||||||
| 言語 | ja | |||||||||||||
| アクセス権 | ||||||||||||||
| アクセス権 | open access | |||||||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||||||
| 著者 |
河野, 知樹
× 河野, 知樹
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| 抄録 | ||||||||||||||
| 内容記述タイプ | Abstract | |||||||||||||
| 内容記述 | Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Clinical management has improved the prognosis of early HCC, but that of advanced HCC remains poor. Sorafenib, an oral multikinase inhibitor, provided a treatment option for advanced-stage HCC, and prolonged the survival and inhibited tumor progression as first-line therapy in patients with advanced HCC. In this study, we investigated if specific microRNAs could act as predictive biomarkers of sorafenib effectiveness and indicate the best time to switch to second-line therapies. Sorafenib inhibited the proliferation of the Li-7, Hep3B, HepG2 and Huh7 liver cancer cell lines (effective group), but not that of the HLE, HLF and ALEX cancer cell lines (non-effective group). A microRNA (miRNA/miR) analysis was performed comparing sorafenib-effective and non-effective cells lines as well as serum samples from patients with HCC from sorafenib-effective (complete response/partial response) and -non-effective (progressive disease) groups before sorafenib administration and detected three differentially-expressed miRNAs that were common among the in vivo and in vitro samples. The increase rate (effective/non-effective) of hsa-miR-30d in the medium was higher than that in the cancer cells. hsa-miR-30d was highly expressed in the serum and exosomes of patients with HCC in the effective group when compared to those of the non-effective group. Additionally, the hsa-miR-30d expression in the medium of cancer cell lines was highly upregulated in the effective group compared with the non-effective group. These results suggested that hsa-miR-30d might be secreted by the cancer cells to the serum through the exosomes. We identified a specific circulating miRNA that is related to refractory HCC under sorafenib therapy. Therefore, hsa-miR-30d might serve as a predictive biomarker for the efficacy of sorafenib therapy in HCC. | |||||||||||||
| 言語 | en | |||||||||||||
| 学位名 | ||||||||||||||
| 言語 | ja | |||||||||||||
| 学位名 | 博士（医学） | |||||||||||||
| 学位授与機関 | ||||||||||||||
| 識別子Scheme | kakenhi | |||||||||||||
| 識別子 | 16201 | |||||||||||||
| 言語 | ja | |||||||||||||
| 機関名 | 香川大学 | |||||||||||||
| 言語 | en | |||||||||||||
| 機関名 | Kagawa University | |||||||||||||
| 学位授与年月日 | ||||||||||||||
| 学位授与年月日 | 2020-06-25 | |||||||||||||
| 学位授与番号 | ||||||||||||||
| 学位授与番号 | 甲第755号 | |||||||||||||
| 権利 | ||||||||||||||
| 言語 | en | |||||||||||||
| 権利情報 | Copyright: © Kohno et al. | |||||||||||||
| 権利 | ||||||||||||||
| 言語 | en | |||||||||||||
| 権利情報Resource | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |||||||||||||
| 権利情報 | This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. | |||||||||||||
| 論文ID（NAID） | ||||||||||||||
| 識別子タイプ | NAID | |||||||||||||
| 関連識別子 | 500001401702 | |||||||||||||
| PubMed番号 | ||||||||||||||
| 識別子タイプ | PMID | |||||||||||||
| 関連識別子 | 32724415 | |||||||||||||
| 関連サイト | ||||||||||||||
| 関連タイプ | isVersionOf | |||||||||||||
| 識別子タイプ | DOI | |||||||||||||
| 関連識別子 | https://doi.org/10.3892/ol.2020.11696 | |||||||||||||
| 関連サイト | ||||||||||||||
| 関連タイプ | isIdenticalTo | |||||||||||||
| 識別子タイプ | URI | |||||||||||||
| 関連識別子 | https://dl.ndl.go.jp/pid/11538246 | |||||||||||||
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| 関連タイプ | hasVersion | |||||||||||||
| 識別子タイプ | URI | |||||||||||||
| 関連識別子 | http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7377167/ | |||||||||||||
| 著者版フラグ | ||||||||||||||
| 出版タイプ | P | |||||||||||||
| 出版タイプResource | http://purl.org/coar/version/c_fa2ee174bc00049f | |||||||||||||
| KEID | ||||||||||||||
| 29005 | ||||||||||||||
