{"created":"2022-08-30T06:35:00.179272+00:00","id":2000666,"links":{},"metadata":{"_buckets":{"deposit":"c9ff3309-4582-4ab9-a33f-3c5eeaccca9a"},"_deposit":{"id":"2000666","owners":[1],"pid":{"revision_id":0,"type":"depid","value":"2000666"},"status":"published"},"_oai":{"id":"oai:niigata-u.repo.nii.ac.jp:02000666","sets":["453:456","471:537:538:1661840400705"]},"author_link":[],"item_1627361970403":{"attribute_name":"出版タイプ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_7_biblio_info_6":{"attribute_name":"書誌情報","attribute_value_mlt":[{"bibliographicIssueDates":{"bibliographicIssueDate":"2021-07","bibliographicIssueDateType":"Issued"},"bibliographicIssueNumber":"7","bibliographicPageEnd":"130","bibliographicPageStart":"119","bibliographicVolumeNumber":"135","bibliographic_titles":[{"bibliographic_title":"新潟医学会雑誌","bibliographic_titleLang":"ja"}]}]},"item_7_description_4":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"【緒言】マイクロサテライト不安定性(High-frequency microsatellite instability: MSI-H)を有する大腸癌は，免疫チェックポイント阻害剤の効果が認められる重要なサブグループである．近年，多数の遺伝子異常(変異，塩基置換，挿入／欠失，コピー数異常，再編成，融合等)を一括して解析するがん遺伝子パネル検査の登場により，各種の固形癌において新たな治療標的となり得る遺伝子異常が明らかになりつつある．本研究の目的は，がん遺伝子パネル検査を実施したMSI-H大腸癌の臨床病理学的特徴および遺伝子異常の特徴を解析し，MSI-H大腸癌に対する新たな治療標的を探索することである．【方法】がん遺伝子パネル検査を実施したStage I-IV大腸癌203例のうち，MSI-H 13例(MSI-H群)とMicrosatellite stable(MSS)36例(MSS群)を対象とした．MSI-H群とMSS群は，傾向スコアマッチング法によって症例を選択した．MSI-H群とMSS群の臨床病理学的特徴，遺伝子異常の発生頻度，遺伝子異常の病的意義を比較した．さらに，MSI-H群13例中12例に対して，PD-L1(Programmed death-ligand 1)免疫組織化学(SP142)を実施し，PD-L1発現陽性症例の臨床病理学的特徴を解析した．【結果】臨床病理学的特徴では，MSI-H群はMSS群と比較して，右側大腸(P=0.048)，髄様増殖有り(P=0.016)，腫瘍内リンパ球浸潤≧10(P<0.001)の頻度が有意に高かった．遺伝子異常では，MSI-H群はMSS群と比較して，BRAF(P<0.01)，PIK3CA(P<0.05)等，20遺伝子で有意に遺伝子異常の発生頻度が有意に高かった．一方で，MSI-H群はMSS群と比較してTP53で遺伝子異常の発生頻度が有意に低かった(P<0.05)．遺伝子異常の病的意義については，Pathogenic(病的)/Likely Pathogenic(おそらく病的)とされた遺伝子異常は，MSI-H群で253か所中49か所(19.4%)，MSS群で320か所中59か所(18.4%)であった．PD-L1免疫組織化学を施行したMSI-H群12症例中6例(50%)がPD-L1発現陽性，6例(50%)がPD-L1発現陰性であった．PD-L1発現陽性症例ではPD-L1発現陰性症例と比較すると，深達度T3，4(P=0.046)，髄様増殖有り(P=0.046)，リンパ管侵襲有り(P=0.003)と有意に関連していた．【結論】MSI-H大腸癌は，MSS大腸癌と比較して異なる遺伝子異常の特徴を有するサブグループである．MSI-H大腸癌では，BRAF変異やPIK3CA変異等，新たな治療標的となり得る遺伝子異常が認められる．MSI-H症例の中には，PD-L1発現陰性症例も認めることから，MSI-H大腸癌に対する免疫チェックポイント阻害剤の選択において，さらなる個別化治療が求められる可能性がある．","subitem_description_language":"ja","subitem_description_type":"Abstract"}]},"item_7_publisher_7":{"attribute_name":"出版者","attribute_value_mlt":[{"subitem_publisher":"新潟医学会","subitem_publisher_language":"ja"}]},"item_7_source_id_11":{"attribute_name":"書誌レコードID","attribute_value_mlt":[{"subitem_source_identifier":"AN00182415","subitem_source_identifier_type":"NCID"}]},"item_7_source_id_9":{"attribute_name":"ISSN","attribute_value_mlt":[{"subitem_source_identifier":"0029-0440","subitem_source_identifier_type":"PISSN"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"平井, 裕美子","creatorNameLang":"ja"},{"creatorName":"Hirai, Yumiko","creatorNameLang":"en"}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_access","date":[{"dateType":"Available","dateValue":"2022-08-30"}],"displaytype":"detail","filename":"135(7)_119-130.pdf","filesize":[{"value":"2.1MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"objectType":"fulltext","url":"https://niigata-u.repo.nii.ac.jp/record/2000666/files/135(7)_119-130.pdf"},"version_id":"e4b93bb7-e36a-437f-b1fa-e50a6cf18d73"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"大腸癌","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"マイクロサテライト不安定性","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"遺伝子異常","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"がん遺伝子パネル検査","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"PD-L1","subitem_subject_language":"en","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":"departmental bulletin paper","resourceuri":"http://purl.org/coar/resource_type/c_6501"}]},"item_title":"マイクロサテライト不安定性を有する大腸癌における遺伝子異常の特徴","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"マイクロサテライト不安定性を有する大腸癌における遺伝子異常の特徴","subitem_title_language":"ja"},{"subitem_title":"Characteristics of Genetic Alteration in Patients with High-frequency Microsatellite Instability in Colorectal Cancer","subitem_title_language":"en"}]},"item_type_id":"7","owner":"1","path":["456","1661840400705"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2022-08-30"},"publish_date":"2022-08-30","publish_status":"0","recid":"2000666","relation_version_is_last":true,"title":["マイクロサテライト不安定性を有する大腸癌における遺伝子異常の特徴"],"weko_creator_id":"1","weko_shared_id":-1},"updated":"2022-12-15T04:36:01.570903+00:00"}