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cells, cell, cancer, gastric, fig, article, google, scholar, tumor, expression, additional, file, gene, data, cas, genes, singlecell, subtypes, endothelial, clusters, cluster, patients, analysis, fibroblasts, bulk, types, samples, survival, rnaseq, tme, activated, immune, fibroblast, found, tissue, response, fcthrc, expressed, macrophages, microenvironment, normal, malignant, cohort, immunotherapy, performed, communication, sequencing, top, myeloid, patient,

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xcl1/xcl2-xcr1 receptor-ligand axis cn/gsa-human/browse/hra002336 hif-1α/cxcr4 signaling pathway gm-csf-pd-l1 pathway chemokine-receptor pairs cxcl1/2/3/5/8–cxcr1/2 heat-shock protein-related program m04-c3 anti-inflammatory macrophages cn/gsa-human/policy/policy single-cell rna-seq integration single-cell rna-seq data applying single-cell rna-seq uk/ena/browser/view/prjeb25780 large-scale expression profiling m11-spp1 anti-inflammatory macrophages single-cell transcriptome profiles bulk/single-cell integration applied conventional cdc1 m16-clec9a tcga-stad rna-seq samples influences colitis-induced tumorigenesis single-cell rna sequencing single-cell rna-seq dissociation-derived batch effect cthrc1-positive fibroblast-specific genes wilcoxon rank-sum test f13-depleted/m16-enriched patients bulk rna-seq datasets full size image mediate anti-pd1 resistance preselected single-cell abundances tumor bulk rna-seq bulk rna-seq data bulk rna-seq data activating wnt/pcp signaling support tumor-infiltrating cytotoxic hla-ii expressing macrophages anti-pd1-treated patients cell type depletion strategies including epstein–barr virus bulk rna-seq samples x-axis represents ligand anti-inflammatory gene signature partition-based graph abstraction fibroblasts-derived vcam1 induced article  google scholar dectin-2–induced ccl2 production m16-clec9a dendritic cells actual single-cell fractions ligand-receptor pair l1r1 anti-inflammatory signatures making 150-bp paired-end reads

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WebPage:
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         headline:Parallel single-cell and bulk transcriptome analyses reveal key features of the gastric tumor microenvironment
         description:The tumor microenvironment (TME) has been shown to strongly influence treatment outcome for cancer patients in various indications and to influence the overall survival. However, the cells forming the TME in gastric cancer have not been extensively characterized. We combine bulk and single-cell RNA sequencing from tumors and matched normal tissue of 24 treatment-naïve GC patients to better understand which cell types and transcriptional programs are associated with malignant transformation of the stomach. Clustering 96,623 cells of non-epithelial origin reveals 81 well-defined TME cell types. We find that activated fibroblasts and endothelial cells are most prominently overrepresented in tumors. Intercellular network reconstruction and survival analysis of an independent cohort imply the importance of these cell types together with immunosuppressive myeloid cell subsets and regulatory T cells in establishing an immunosuppressive microenvironment that correlates with worsened prognosis and lack of response in anti-PD1-treated patients. In contrast, we find a subset of IFNγ activated T cells and HLA-II expressing macrophages that are linked to treatment response and increased overall survival. Our gastric cancer single-cell TME compendium together with the matched bulk transcriptome data provides a unique resource for the identification of new potential biomarkers for patient stratification. This study helps further to elucidate the mechanism of gastric cancer and provides insights for therapy.
         datePublished:2022-12-22T00:00:00Z
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            Tumor microenvironment
            Gastric cancer
            Single-cell RNA transcriptomics
            Animal Genetics and Genomics
            Human Genetics
            Plant Genetics and Genomics
            Microbial Genetics and Genomics
            Bioinformatics
            Evolutionary Biology
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      headline:Parallel single-cell and bulk transcriptome analyses reveal key features of the gastric tumor microenvironment
      description:The tumor microenvironment (TME) has been shown to strongly influence treatment outcome for cancer patients in various indications and to influence the overall survival. However, the cells forming the TME in gastric cancer have not been extensively characterized. We combine bulk and single-cell RNA sequencing from tumors and matched normal tissue of 24 treatment-naïve GC patients to better understand which cell types and transcriptional programs are associated with malignant transformation of the stomach. Clustering 96,623 cells of non-epithelial origin reveals 81 well-defined TME cell types. We find that activated fibroblasts and endothelial cells are most prominently overrepresented in tumors. Intercellular network reconstruction and survival analysis of an independent cohort imply the importance of these cell types together with immunosuppressive myeloid cell subsets and regulatory T cells in establishing an immunosuppressive microenvironment that correlates with worsened prognosis and lack of response in anti-PD1-treated patients. In contrast, we find a subset of IFNγ activated T cells and HLA-II expressing macrophages that are linked to treatment response and increased overall survival. Our gastric cancer single-cell TME compendium together with the matched bulk transcriptome data provides a unique resource for the identification of new potential biomarkers for patient stratification. This study helps further to elucidate the mechanism of gastric cancer and provides insights for therapy.
      datePublished:2022-12-22T00:00:00Z
      dateModified:2022-12-22T00:00:00Z
      pageStart:1
      pageEnd:25
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      sameAs:https://doi.org/10.1186/s13059-022-02828-2
      keywords:
         Tumor microenvironment
         Gastric cancer
         Single-cell RNA transcriptomics
         Animal Genetics and Genomics
         Human Genetics
         Plant Genetics and Genomics
         Microbial Genetics and Genomics
         Bioinformatics
         Evolutionary Biology
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      author:
            name:Boxi Kang
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                  name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University
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            name:Jordi Camps
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            type:Person
            name:Biao Fan
            affiliation:
                  name:Peking University Cancer Hospital and Institute
                  address:
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         type:PostalAddress
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University
      address:
         name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
         type:PostalAddress
      name:Research & Early Development Oncology, Bayer AG
      address:
         name:Immuno Oncology, Research & Early Development Oncology, Bayer AG, Berlin, Germany
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      address:
         name:Biomedical Data Science, Research & Early Development Oncology, Bayer US, Cambridge, USA
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      name:Peking University People’s Hospital
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         name:Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, China
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      address:
         name:Laboratory of Surgical Oncology, Peking University People’s Hospital, Beijing, China
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      address:
         name:Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, China
         type:PostalAddress
      name:Peking University People’s Hospital
      address:
         name:Laboratory of Surgical Oncology, Peking University People’s Hospital, Beijing, China
         type:PostalAddress
      name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research
      address:
         name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
         type:PostalAddress
      name:Peking University People’s Hospital
      address:
         name:Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, China
         type:PostalAddress
      name:Peking University People’s Hospital
      address:
         name:Laboratory of Surgical Oncology, Peking University People’s Hospital, Beijing, China
         type:PostalAddress
      name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research
      address:
         name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
         type:PostalAddress
      name:Peking University Cancer Hospital and Institute
      address:
         name:Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
         type:PostalAddress
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University
      address:
         name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
         type:PostalAddress
      name:Peking-Tsinghua Centre for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University
      address:
         name:Peking-Tsinghua Centre for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
         type:PostalAddress
      name:Research & Early Development Oncology, Bayer AG
      address:
         name:Oncology Precision Medicine, Research & Early Development Oncology, Bayer AG, Berlin, Germany
         type:PostalAddress
ImageObject:
      url:https://www.springernature.com/app-sn/public/images/logo-springernature.png
Person:
      name:Boxi Kang
      affiliation:
            name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University
            address:
               name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
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      name:Jordi Camps
      affiliation:
            name:Biomedical Data Science, Research & Early Development Oncology, Bayer AG
            address:
               name:Biomedical Data Science, Research & Early Development Oncology, Bayer AG, Berlin, Germany
               type:PostalAddress
            type:Organization
      name:Biao Fan
      affiliation:
            name:Peking University Cancer Hospital and Institute
            address:
               name:Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
               type:PostalAddress
            type:Organization
      name:Hongpeng Jiang
      affiliation:
            name:Beijing Friendship Hospital, Capital Medical University
            address:
               name:Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
               type:PostalAddress
            type:Organization
            name:Peking University People’s Hospital
            address:
               name:Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, China
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      affiliation:
            name:Biomedical Data Science, Research & Early Development preMed, Bayer AG
            address:
               name:Biomedical Data Science, Research & Early Development preMed, Bayer AG, Wuppertal, Germany
               type:PostalAddress
            type:Organization
      name:Xueda Hu
      affiliation:
            name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University
            address:
               name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Shishang Qin
      affiliation:
            name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University
            address:
               name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      name:Dennis Kirchhoff
      affiliation:
            name:Research & Early Development Oncology, Bayer AG
            address:
               name:Immuno Oncology, Research & Early Development Oncology, Bayer AG, Berlin, Germany
               type:PostalAddress
            type:Organization
      name:Derek Y. Chiang
      affiliation:
            name:Biomedical Data Science, Research & Early Development Oncology, Bayer US
            address:
               name:Biomedical Data Science, Research & Early Development Oncology, Bayer US, Cambridge, USA
               type:PostalAddress
            type:Organization
      name:Shan Wang
      affiliation:
            name:Peking University People’s Hospital
            address:
               name:Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, China
               type:PostalAddress
            type:Organization
            name:Peking University People’s Hospital
            address:
               name:Laboratory of Surgical Oncology, Peking University People’s Hospital, Beijing, China
               type:PostalAddress
            type:Organization
            name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research
            address:
               name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
               type:PostalAddress
            type:Organization
      name:Yingjiang Ye
      affiliation:
            name:Peking University People’s Hospital
            address:
               name:Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, China
               type:PostalAddress
            type:Organization
            name:Peking University People’s Hospital
            address:
               name:Laboratory of Surgical Oncology, Peking University People’s Hospital, Beijing, China
               type:PostalAddress
            type:Organization
            name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research
            address:
               name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
               type:PostalAddress
            type:Organization
      name:Zhanlong Shen
      affiliation:
            name:Peking University People’s Hospital
            address:
               name:Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, China
               type:PostalAddress
            type:Organization
            name:Peking University People’s Hospital
            address:
               name:Laboratory of Surgical Oncology, Peking University People’s Hospital, Beijing, China
               type:PostalAddress
            type:Organization
            name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research
            address:
               name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Zhaode Bu
      affiliation:
            name:Peking University Cancer Hospital and Institute
            address:
               name:Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Zemin Zhang
      affiliation:
            name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University
            address:
               name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
            name:Peking-Tsinghua Centre for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University
            address:
               name:Peking-Tsinghua Centre for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Helge G. Roider
      affiliation:
            name:Research & Early Development Oncology, Bayer AG
            address:
               name:Oncology Precision Medicine, Research & Early Development Oncology, Bayer AG, Berlin, Germany
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:Biomedical Data Science, Research & Early Development Oncology, Bayer AG, Berlin, Germany
      name:Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
      name:Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China
      name:Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, China
      name:Biomedical Data Science, Research & Early Development preMed, Bayer AG, Wuppertal, Germany
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:Immuno Oncology, Research & Early Development Oncology, Bayer AG, Berlin, Germany
      name:Biomedical Data Science, Research & Early Development Oncology, Bayer US, Cambridge, USA
      name:Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, China
      name:Laboratory of Surgical Oncology, Peking University People’s Hospital, Beijing, China
      name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
      name:Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, China
      name:Laboratory of Surgical Oncology, Peking University People’s Hospital, Beijing, China
      name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
      name:Department of Gastroenterological Surgery, Peking University People’s Hospital, Beijing, China
      name:Laboratory of Surgical Oncology, Peking University People’s Hospital, Beijing, China
      name:Beijing Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China
      name:Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China
      name:BIOPIC, Beijing Advanced Innovation Centre for Genomics, and School of Life Sciences, Peking University, Beijing, China
      name:Peking-Tsinghua Centre for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China
      name:Oncology Precision Medicine, Research & Early Development Oncology, Bayer AG, Berlin, Germany

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