{"title":"Integrating scRNA-seq and Visium HD for the analysis of the tumor microenvironment in the progression of colorectal cancer.","authors":"Chun Wang, Mengying Lu, Cuimin Chen, Jiajun Chen, Yusi Cai, Hao Wang, Lili Tao, Weihua Yin, Jiakang Chen","doi":"10.1016/j.intimp.2024.113752","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Colorectal cancer (CRC) development is a complex, multi-stage process, transitioning from normal to adenomatous tissue, and then to invasive carcinoma. Despite research, there's a knowledge gap on using high-resolution spatial omics to understand CRC's tumor microenvironment dynamics.</p><p><strong>Methods: </strong>We used single-cell transcriptomics to study major biological changes and cell interactions in CRC progression. Additionally, high-resolution spatial transcriptomics helped us examine the spatial distribution of cells with significant pathway changes, offering insights into the tumor microenvironment's development throughout CRC stages.</p><p><strong>Results: </strong>In the progression of CRC, plasma cells, neutrophils, and fibroblasts exhibit the most significant changes in hallmark pathways, while epithelial cells show the most pronounced alterations in metabolic pathways. We also identified a population of NOTUM + epithelial cells and IGHG1/3 + plasma cells that are concentrated at the boundary between normal tissue and adenomas. Pathway analysis further suggests that these NOTUM + cells activate numerous cancer-related pathways, despite the absence of significant pathological morphological changes. Additionally, we conducted a targeted drug prediction analysis to identify potential therapeutic agents for NOTUM-expressing epithelial cells.</p><p><strong>Conclusions: </strong>Analyzing scRNA-seq and Visium HD data, we found that IGHG1/3 + plasma cells and tumor-associated neutrophil (TANs) may significantly affect colorectal tissue transformation from normal to adenoma and carcinoma. These cells are concentrated at the transition between normal and adenomatous tissue. We also found NOTUM-expressing cells at the edge of normal and adenomatous areas, possibly indicating a morphological transition as normal cells evolve into adenoma cells.</p>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":"145 ","pages":"113752"},"PeriodicalIF":4.8000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.intimp.2024.113752","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/6 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Colorectal cancer (CRC) development is a complex, multi-stage process, transitioning from normal to adenomatous tissue, and then to invasive carcinoma. Despite research, there's a knowledge gap on using high-resolution spatial omics to understand CRC's tumor microenvironment dynamics.
Methods: We used single-cell transcriptomics to study major biological changes and cell interactions in CRC progression. Additionally, high-resolution spatial transcriptomics helped us examine the spatial distribution of cells with significant pathway changes, offering insights into the tumor microenvironment's development throughout CRC stages.
Results: In the progression of CRC, plasma cells, neutrophils, and fibroblasts exhibit the most significant changes in hallmark pathways, while epithelial cells show the most pronounced alterations in metabolic pathways. We also identified a population of NOTUM + epithelial cells and IGHG1/3 + plasma cells that are concentrated at the boundary between normal tissue and adenomas. Pathway analysis further suggests that these NOTUM + cells activate numerous cancer-related pathways, despite the absence of significant pathological morphological changes. Additionally, we conducted a targeted drug prediction analysis to identify potential therapeutic agents for NOTUM-expressing epithelial cells.
Conclusions: Analyzing scRNA-seq and Visium HD data, we found that IGHG1/3 + plasma cells and tumor-associated neutrophil (TANs) may significantly affect colorectal tissue transformation from normal to adenoma and carcinoma. These cells are concentrated at the transition between normal and adenomatous tissue. We also found NOTUM-expressing cells at the edge of normal and adenomatous areas, possibly indicating a morphological transition as normal cells evolve into adenoma cells.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.