{"id":"hum0402","version":1,"url":"https://humandbs.dbcls.jp/research/hum0402/v1","datePublished":"2024-04-12","versions":[{"version":1,"datePublished":"2024-04-12"}],"title":{"ja":"大腸多段階発がん進化の過程においてドライバー変異を生じる機序の解明","en":"Elucidation of the mechanisms that give rise to driver mutations in colorectal carcinogenesis"},"summary":{"aims":{"ja":"近年、single cell RNA sequence解析により、大腸がん細胞と間質細胞における細胞間相互作用が解析されてきたが、がんの早期における腺腫から発現する重要ながん微小環境、特に免疫寛容獲得機構に関してはまだ明らかになっていない。公共データベースより入手したシングルセル解析と空間的トランスクリプトーム解析を統合することにより、腺腫がん境界部における免疫寛容およびがん微小環境の形成について調べた。この解析により、早期がん細胞が共局在する免疫細胞および細胞間相互作用を明らかにし、免疫から逃避するメカニズムを明らかにすることによって新たな治療標的分子を探索する。","en":"Recently, single cell RNA sequencing has been used to analyze cell-cell interactions between colon cancer cells and stromal cells. However, the important cancer microenvironment during early cancer development from adenomas, especially the mechanism of immune tolerance acquisition, is unclear. In this study, we investigated immune tolerance and the formation of the tumor microenvironment at the adenoma-cancer interface by integrating single-cell and spatial transcriptome analyses obtained from public databases. By integrating scRNA-seq of colorectal cancer and spatial transcriptome analysis in carcinoma in adenoma tissues, we investigated immune tolerance and tumor microenvironment formation at the adenoma-tumor interface thereby searching for new therapeutic target molecules."},"methods":{"ja":"ホルマリン固定パラフィン包埋標本（FFPE）から5μm厚切片を作成し、Visium Spatial Gene Expression Reagent Kits for FFPEユーザーガイドに従い、Visium Spatial Gene Expression Slide Kit（10x Genomics）を用いて処理した。切片をH&E染色して画像化した後、MGI DNBSEQ-G400システムを用いて捕捉したプローブライブラリーをシーケンスし、リードをデマルチプレックスした。","en":"Formalin-fixed paraffin-embedded (FFPE) samples were used to prepare for spatial transcriptomic construction and sequencing. 5μm thick sections were prepared from the FFPE samples and processed using Visium Spatial Gene Expression Slide Kit (10x Genomics) according to the Visium Spatial Gene Expression Reagent Kits for FFPE User Guide. First, sections were stained with H&E and imaged followed by probe hybridization and ligation. Then, the captured probe library was sequenced using an MGI DNBSEQ-G400 system for 28, 10, 10, and 50 cycles for Read 1, i7, i5, and Read2 sequences respectively."},"targets":{"ja":"発がん機転ACS（adenocarcinoma sequence）を背景とした大腸がん症例","en":"Patients with colorectal cancer with a background of adenocarcinoma sequence (ACS)"},"url":{"ja":null,"en":null}},"listingSummary":{"methods":{"ja":"発現\n病理画像","en":"Expression profiling, Histological imaging"},"targets":{"ja":"大腸癌：4症例\n（日本人）","en":"colorectal cancer: 4 cases\n(Japanese)"},"typeOfData":{"ja":"NGS\n（Visium Spatial Gene Expression）\n病理画像","en":"NGS\n(Visium Spatial Gene Expression)\nHistological image"}},"releaseNote":{"ja":"adenocarcinoma sequence（良性のポリープである腺腫が少しずつ悪性化し、ついには大腸がんになる説）を背景とした大腸がん症例の腫瘍組織に対して実施した空間トランスクリプトーム解析データを提供する（fastq、tif、png、json、csvファイル）。","en":"RNAs extracted from specimens sectioned into 5μm sections were used for Visium Spatial Gene Expression Assay. Fastq files, tif and png files (histological image), json files and csv files (position information) are provided."},"dataProviders":[{"name":{"ja":"三森 功士","en":"Koshi Mimori"},"organization":{"name":{"ja":"九州大学病院別府病院 外科","en":"Department of Surgery, Kyushu University Beppu Hospital"}}}],"researchProjects":[{"name":{"ja":"大腸発癌におけるドライバー変異の発生機序の解明","en":"Elucidation of the mechanisms that give rise to driver mutations in colorectal carcinogenesis"},"url":{"ja":null,"en":null}}],"grants":[{"title":{"ja":"大腸がんctDNAの術後早期再発診断システム開発と再発への進化系統樹の臨床的意義","en":"Clinical significance of evolutionary phylogenetic tree for colorectal cancer ctDNA for early postoperative recurrence diagnostic system development and recurrence"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["JP21K07179"]},{"title":{"ja":"多領域シークエンスと進化シミュレーションによる大腸がん腫瘍内ダイバーシティの解明","en":"Diversity in colorectal cancer tumors by multi-domain sequencing and evolutionary simulation"},"agency":{"ja":"科学研究費助成事業 新学術領域研究（研究領域提案型）","en":"KAKENHI Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)"},"grantIds":["JP20H05039"]},{"title":{"ja":"大腸初期病変から進行がんへの真の進化様式解明と治療法の確立","en":"Elucidation of the pattern of progression from early colorectal tumor lesions to advanced cancer and establishment of treatment methods"},"agency":{"ja":"科学研究費助成事業 基盤研究（B）","en":"KAKENHI Grant-in-Aid for Scientific Research (B)"},"grantIds":["JP19H03715"]},{"title":{"ja":"ゲノム進化モデルにより同定された大腸癌におけるタンパク翻訳開始点制御の異常の解明","en":"Aberrant regulation of protein translation start sites in colorectal cancer identified by genome evolution model"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["JP19K09176"]},{"title":{"ja":"ctDNAメチル化検出を実装する新たなアプローチによる大腸癌再発早期診断法の確立","en":"New approach to implement ctDNA methylation detection for early diagnosis of colorectal cancer recurrence"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["JP20K08930"]},{"title":{"ja":"大腸がん細胞との共局在により悪性度と免疫寛容を獲得するがん微小環境の解明","en":"Malignant transformation and immune tolerance in the cancer microenvironment by colocalization with colon cancer cells and other cells"},"agency":{"ja":"科学研究費助成事業 基盤研究（B）","en":"KAKENHI Grant-in-Aid for Scientific Research (B)"},"grantIds":["JP22H02903"]},{"title":{"ja":"空間的シングルセル解析による大腸線癌から発がん過程に於ける免疫寛容獲得機構の解明","en":"Spatial single-cell analysis of the mechanism of immune tolerance in early colorectal carcinogenesis"},"agency":{"ja":"科学研究費助成事業 基盤研究（C）","en":"KAKENHI Grant-in-Aid for Scientific Research (C)"},"grantIds":["JP23K08074"]},{"title":{"ja":"難治性がんにおけるエピジェネティックな多様性・環境適応創生機構の解明に基づく新たな治療法開発","en":"Development of new therapies based on the elucidation of epigenetic diversity and environmental adaptive genesis mechanisms in refractory cancer"},"agency":{"ja":"日本医療研究開発機構（AMED） 次世代がん医療創生研究事業（P-CREATE）","en":"Project for Cancer Research and Therapeutic Evolution (P-CREATE), Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP22ama221501"]},{"title":{"ja":"国際共同研究に資する大規模日本人がんゲノム・オミックス・臨床データ統合解析とゲノム医療推進に向けた知識基盤構築","en":"Integrated analysis of large-scale Japanese cancer genome, omics, and clinical data for international collaborative research and construction of knowledge base for the promotion of genomic medicine"},"agency":{"ja":"日本医療研究開発機構（AMED） 革新的がん医療実用化研究事業","en":"Practical Research for Innovative Cancer Control, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP20ck0106547"]},{"title":{"ja":"大腸がん微小転移巣形成機構の理解による新規予防治療戦略の確立","en":"Novel preventive treatment strategies by understanding the mechanisms of micrometastasis formation in colorectal cancer"},"agency":{"ja":"日本医療研究開発機構（AMED） 革新的がん医療実用化研究事業","en":"Practical Research for Innovative Cancer Control, Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP20ck0106541"]},{"title":{"ja":"難治がん特異的エピゲノム変異を標的にしたctDNA検出法の確立","en":"Establishment of a ctDNA detection method targeting intractable cancer-specific epigenomic mutations"},"agency":{"ja":"日本医療研究開発機構（AMED） 次世代がん医療創生研究事業（P-CREATE）","en":"Project for Cancer Research and Therapeutic Evolution (P-CREATE), Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP20cm0106475"]},{"title":{"ja":"微小環境多様性に連動する難治がんの分子遺伝学的多様性創成機構の解明と新たながん治療法・予測医療技術の開発","en":"Elucidation of molecular genetic diversity creation mechanism of intractable cancer linked to microenvironmental diversity and development of new cancer therapies and predictive medical technologies"},"agency":{"ja":"日本医療研究開発機構（AMED） 次世代がん医療創生研究事業（P-CREATE）","en":"Project for Cancer Research and Therapeutic Evolution (P-CREATE), Japan Agency for Medical Research and Development (AMED)"},"grantIds":["JP19cm0106504"]}],"relatedPublications":[{"title":"Spatial and single-cell colocalisation analysis reveals MDK-mediated immunosuppressive environment with regulatory T cells in colorectal carcinogenesis","doi":"https://doi.org/10.1016/j.ebiom.2024.105102","datasets":["DRA016537","E-GEAD-622"]}],"datasets":["DRA016537","E-GEAD-622"],"controlledAccessUsers":[]}