2020 Fiscal Year Final Research Report

Analysis of single-cell transcriptome with Drop-seq for heterogeneity in the tumor microenvironment derived from digestive cancers.

Research Project

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Project/Area Number	19K22664
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research Institution	Kyushu University
Principal Investigator	OHUCHIDA Kenoki 九州大学, 大学病院, 講師 (20452708)
Co-Investigator(Kenkyū-buntansha)	藤田逸人九州大学, 医学研究院, 共同研究員 (40611281) 森山大樹九州大学, 大学病院, 准教授 (70586859) 永吉絹子九州大学, 大学病院, 助教 (90761015)
Project Period (FY)	2019-06-28 – 2021-03-31
Keywords	消化器癌 / 胃癌 / 食道癌 / シングルセル解析 / 腫瘍微小環境 / heterogeneity
Outline of Final Research Achievements	This study was started to elucidate heterogeneity in digestive cancers by single-cell transcriptome with Drop-seq. About gastric and esophageal cancers, we created 20 cases of scRNA-sequencing data for normal mucosae, tumor sites and lymph nodes for each. In the analysis of data with esophageal cancer, “exhausted” T cells were detected more in the tumor sites than in the normal mucosae, and we considered that the T cells function decreased with carcinogenesis. Plasma cells were found more in the tumor lesions, suggesting that many antibodies were produced in the tumor microenvironment. Furthermore, comparing gastric cancers with esophageal cancers, we think that the activation of B cells was promoted more in the gastric cancers. In short, with scRNA-seq, we could analyze the heterogeneity of the digestive tumor microenvironment in detail.
Free Research Field	医歯薬学
Academic Significance and Societal Importance of the Research Achievements	本研究は革新的な技術であるDrop-seqを基盤としたシングルセル解析を用いることで、これまで詳細が不明であった消化器癌の腫瘍微小環境内の不均一性を解明することを目的とした。従来のBulkでのRNA-seqでの解析では評価できなかった各細胞の不均一性をシングルセル解析では詳細に解析することが可能であった。特に免疫細胞に関しての単一細胞レベルの機能的評価が可能となり、発癌過程の解明や、免疫チェックポイントを中心とした新たな治療法の確立につながると考えられる。