{"id":"hum0356","version":1,"url":"https://humandbs.dbcls.jp/research/hum0356/v1","datePublished":"2022-12-20","versions":[{"version":1,"datePublished":"2022-12-20"},{"version":2,"datePublished":"2024-05-31"}],"title":{"ja":"大腸発がんにおける遺伝子変化の解明と間質の臨床的意義の確立","en":"Elucidation of genetic alterations in colorectal carcinogenesis and establishment of clinical significance of interstitial"},"summary":{"aims":{"ja":"近年、single cell RNA sequence解析により、adenocarcinoma sequenceを背景とする大腸がんの腫瘍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、空間的な視点が欠落していた。そのため、がん早期において重要ながん微小環境、特に免疫寛容の獲得機構に関しては明らかではない。今回は、公共データベースより得られたシングルセル解析データと空間的トランスクリプトーム解析データの統合解析により、腺腫がん境界部における免疫寛容および腫瘍微小環境の形成について調べた。この解析により、早期におけるがん細胞と免疫細胞との共局在状況や、浸潤先進部における細胞間相互作用について解析することで、免疫から逃避するメカニズムを明らかにし、新たな治療標的分子を探索する。","en":"Recently, single-cell RNA sequencing analysis has been used to analyze cell-cell interactions between colorectal cancer cells and stromal cells in colorectal cancer patients with an adenocarcinoma sequence background. 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, and thereby searching for new therapeutic target molecules."},"methods":{"ja":"手術による摘出検体を液体窒素にて凍結させた。その後、キャプチャ領域に合わせて切断し、クライオスタットを用いて10μmの切片に切り出した。この標本をVisium Spatialスライドに載せ、使用するまで-80 ℃で保存した。組織を透過酵素（10x Genomics: 2000214）で50分間透過処理し、0.1×SSCバッファー（Sigma-Aldrich）で洗浄し、画像化した。全ての工程は、製造元のプロトコール（CG000240 Rev D、CG000160 Rev A）に従って行った。","en":"Surgical specimens were frozen in liquid nitrogen. Specimens were cut according to the capture area and sectioned into 10-μm sections using a cryostat. The specimens were placed on Visium Spatial slides and stored at -80 °C until use. Tissues were permeabilized with permeabilization enzyme (10x Genomics: 2000214) for 50 min, washed with 0.1 x SSC buffer (Sigma-Aldrich), and imaged. All steps were performed according to the manufacturer's protocol (CG000240 Rev D, CG000160 Rev A)."},"targets":{"ja":"adenocarcinoma sequenceを背景とした大腸がん症例","en":"A patient with colorectal cancer with a background of adenocarcinoma sequence"},"url":{"ja":null,"en":null}},"listingSummary":{},"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fastq、tif、png、csvファイルにて提供する。","en":"RNAs extracted from specimens sectioned into 10-μm sections were used for Visium Spatial Gene Expression Assay. Fastq files, tif files (histological image for Visium Spatial Gene Expression Assay), and a tsv file 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":"大腸発がんにおける遺伝子変化の解明と間質の臨床的意義の確立","en":"Elucidation of genetic alterations in colorectal carcinogenesis and establishment of clinical significance of interstitial"},"url":{"ja":[{"url":"https://www.beppu.kyushu-u.ac.jp/geka/labo/reseach/","text":"https://www.beppu.kyushu-u.ac.jp/geka/labo/reseach/"}],"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":["21K07179"]},{"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":"Understanding Diversity within 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":["20H05039"]},{"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 true evolutionary pattern from early colorectal 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":["19H03715"]},{"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 Models"},"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":["19K09176"]},{"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":"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":"Establishment of early diagnosis of colorectal cancer recurrence by a new approach implementing ctDNA methylation detection"},"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":["20K08930"]},{"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"]},{"title":{"ja":"大腸がん細胞の多段階悪性化が制御する微小環境形成ネットワーク機構の解明と新規予防治療戦略の確立","en":"Elucidation of microenvironmental network mechanisms regulating multistep malignant transformation of colorectal cancer cells and establishment of novel preventive therapeutic strategies"},"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":["JP19ck0106259"]}],"relatedPublications":[{"title":"spatial and single-cell transcriptomics to decipher the cellular society containing HLA-G+ cancer cells and SPP1+ macrophages in colorectal cancer","doi":"https://doi.org/10.1016/j.celrep.2022.111929","datasets":["DRA015288","E-GEAD-579"]},{"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":["DRA016520","E-GEAD-619"]}],"datasets":["DRA015288","E-GEAD-579"],"controlledAccessUsers":[]}