{"created":"2022-04-04T06:58:58.071565+00:00","id":2000297,"links":{},"metadata":{"_buckets":{"deposit":"c26a2286-9426-4d37-aa5f-eb4a02558b02"},"_deposit":{"id":"2000297","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"2000297"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:02000297","sets":["453:455","471:561:562"]},"author_link":[],"control_number":"2000297","item_6_date_granted_51":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2021-03-23"}]},"item_6_degree_grantor_49":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"新潟大学"},{"subitem_degreegrantor_language":"en","subitem_degreegrantor_name":"Niigata University"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"13101","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_6_degree_name_48":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_6_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"【目的】次世代シークエンサー(NGS)の出現により癌関連遺伝子変異・転座の網羅的な検出が可能になった．しかしながら，非小細胞肺癌患者において再発・予後などに関連する臨床的に重要な癌関連遺伝子変異は完全には解明されていない．本研究では，NGSを用いて癌関連遺伝子変異の検索を行い，手術後の再発・予後および再発時の化学療法効果予測の観点から肺腺癌患者において臨床的に有用な癌関連遺伝子変異を明らかにすることを目的とした．【対象・方法】2008年1月から2014年12月までに新潟大学医歯学総合病院で原発性肺癌に対して手術が施行された患者の中で，以下の適格規準を満たす患者から任意に対象を選択した．①肺葉切除術以上が施行され完全切除であった，②ホルマリン固定パラフィン包埋切片で20%以上の腫瘍部分が存在した，③胸部薄切CTで腫瘍最大径に対する充実濃度の割合が0.5以上であった，④150ng以上のDNAが抽出できた．最終的に63例が本研究の対象となった．癌関連遺伝子変異・臨床病理学的因子の再発・予後への影響と，癌関連遺伝子変異の有無で再発時化学療法の効果予測ができるかを統計学的に検討した．【結果】術後観察期間中央値は62.8ヶ月で，男性43例／女性20例，年齢中央値66歳であった．単変量解析で，サイクリン依存性キナーゼ阻害因子2B(CDKN2B)野生型が変異型と比較して無再発生存率が有意に高かったが，全生存率では有意差を認めなかった．多変量解析では，病理学的StageIII期(ハザード比2.218，p=0.020)とCDKN2B変異型(ハザード比2.814，p=0.002)が独立した再発予測因子であった．全生存に対してはイベント数が少なく多変量解析は行えなかった．再発治療に関して13例でペメトレキセドが投与されていたが，サイクリン依存性キナーゼ阻害因子1B(CDKN1B)変異型が野生型と比較して無増悪生存期間が有意に長く，それぞれの無増悪生存期間中央値は18.0ヶ月と4.1ヶ月であった(p=0.014)．奏功割合はCDKN1B変異型では5例中3例(60%)でCDKN1B野生型では8例中2例(25%)であった．PDが4例であったが，全例CDKN1B野生型であった．【結論】肺腺癌患者において，CDKN2B変異型が術後再発予測因子である可能性とCDKN1B野生型がペメトレキセド治療抵抗性予測に有用な可能性が示唆された．NGSはドライバー遺伝子変異・転座だけでなく，CDKN1B変異型やCDKN2B変異型のような臨床的に重要な可能性のある遺伝子変異の同定も可能である．","subitem_description_language":"ja","subitem_description_type":"Abstract"}]},"item_6_description_53":{"attribute_name":"学位記番号","attribute_value_mlt":[{"subitem_description":"新大院博(医)第992号","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_6_dissertation_number_52":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第4838号"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open 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Tatsuya","creatorNameLang":"en"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"date":[{"dateType":"Available","dateValue":"2022-04-04"}],"displaytype":"detail","filename":"r2nmk992.pdf","filesize":[{"value":"656KB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"本文","objectType":"fulltext","url":"https://niigata-u.repo.nii.ac.jp/record/2000297/files/r2nmk992.pdf"},"version_id":"72606caa-901b-4461-ba97-cee891b6f2a5"},{"date":[{"dateType":"Available","dateValue":"2022-04-04"}],"displaytype":"detail","filename":"r2nmk992_a.pdf","filesize":[{"value":"545KB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"要旨","objectType":"abstract","url":"https://niigata-u.repo.nii.ac.jp/record/2000297/files/r2nmk992_a.pdf"},"version_id":"712efc46-ee8b-4456-909a-25e5e99dc91f"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"肺腺癌","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"次世代シークエンサー","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"サイクリン依存性キナーゼ阻害因子1B","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"サイクリン依存性キナーゼ阻害因子2B","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"ペメトレキセド","subitem_subject_language":"ja","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral 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