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      Identification of gene signatures associated with ulcerative colitis and the association with immune infiltrates in colon cancer

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          Abstract

          Background

          Inflammatory bowel diseases, including ulcerative colitis (UC) and Crohn’s disease, are some of the most common inflammatory disorders of the gastrointestinal tract. The dysfunction of the immune system in the intestines is suggested to be the underlying cause of the pathogenesis of UC. However, the mechanisms regulating these dysfunctional immune cells and inflammatory phenotypes are still unclear.

          Methods

          The differential expression analysis on microarray datasets were performed including GSE24287, GSE87466, GSE102133, and GSE107499, including 376 samples. “Gene Ontology” and “Kyoto Encyclopedia of Genes and Genomes” pathway enrichment analyses were conducted to identify the common differentially expressed genes (DEGs) in these datasets and explore their underlying biological mechanisms. Further algorithms like “Cell-type Identification by Estimating Relative Subsets of RNA Transcripts” were used to determine the infiltration status of immune cells in patients with UC. “Cytoscape” and “Gene Set Enrichment Analysis” were used to screen for hub genes and to investigate their biological mechanisms. The Tumor Immune Estimation Resource database was used to study the correlation between hub genes and infiltrating immune cells in patients with UC. A total of three hub genes, CCL3, MMP3, and TIMP1, were identified using Cytoscape.

          Results

          A positive correlation was observed between these hub genes and patients with active UC. These genes served as a biomarker for active UC. Moreover, a decrease in CCL3, MMP3, and TIMP1 expression was observed in the mucosa of the intestine of patients with active UC who responded to Golimumab therapy. In addition, results show a significant positive correlation between CCL3, MMP3, and TIMP1 expression and different immune cell types including dendritic cells, macrophages, CD8+ T cells, and neutrophils in patients with colon cancer. Moreover, CCL3, MMP3, and TIMP1 expression were strongly correlated with different immune cell markers.

          Conclusion

          Study results show the involvement of hub genes like CCL3, MMP3, and TIMP1 in the pathogenesis of UC. These genes could serve as a novel pharmacological regulator of UC. These could be used as a therapeutic target for treating patients with UC and may serve as biomarkers for immune cell infiltration in colon cancer.

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          Most cited references43

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          Hallmarks of Cancer: The Next Generation

          The hallmarks of cancer comprise six biological capabilities acquired during the multistep development of human tumors. The hallmarks constitute an organizing principle for rationalizing the complexities of neoplastic disease. They include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis. Underlying these hallmarks are genome instability, which generates the genetic diversity that expedites their acquisition, and inflammation, which fosters multiple hallmark functions. Conceptual progress in the last decade has added two emerging hallmarks of potential generality to this list-reprogramming of energy metabolism and evading immune destruction. In addition to cancer cells, tumors exhibit another dimension of complexity: they contain a repertoire of recruited, ostensibly normal cells that contribute to the acquisition of hallmark traits by creating the "tumor microenvironment." Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer. Copyright © 2011 Elsevier Inc. All rights reserved.
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            Metascape provides a biologist-oriented resource for the analysis of systems-level datasets

            A critical component in the interpretation of systems-level studies is the inference of enriched biological pathways and protein complexes contained within OMICs datasets. Successful analysis requires the integration of a broad set of current biological databases and the application of a robust analytical pipeline to produce readily interpretable results. Metascape is a web-based portal designed to provide a comprehensive gene list annotation and analysis resource for experimental biologists. In terms of design features, Metascape combines functional enrichment, interactome analysis, gene annotation, and membership search to leverage over 40 independent knowledgebases within one integrated portal. Additionally, it facilitates comparative analyses of datasets across multiple independent and orthogonal experiments. Metascape provides a significantly simplified user experience through a one-click Express Analysis interface to generate interpretable outputs. Taken together, Metascape is an effective and efficient tool for experimental biologists to comprehensively analyze and interpret OMICs-based studies in the big data era.
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              NCBI GEO: archive for functional genomics data sets—update

              The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) is an international public repository for high-throughput microarray and next-generation sequence functional genomic data sets submitted by the research community. The resource supports archiving of raw data, processed data and metadata which are indexed, cross-linked and searchable. All data are freely available for download in a variety of formats. GEO also provides several web-based tools and strategies to assist users to query, analyse and visualize data. This article reports current status and recent database developments, including the release of GEO2R, an R-based web application that helps users analyse GEO data.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                19 January 2023
                2023
                : 14
                : 1086898
                Affiliations
                [1] 1 Department of Clinical Laboratory, Xuzhou Central Hospital, Xuzhou Institute of Medical Sciences, Xuzhou Clinical School of Xuzhou Medical University , Xuzhou, Jiangsu, China
                [2] 2 Department of Gastrointestinal Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University , Xuzhou, Jiangsu, China
                [3] 3 Department of Cell Biology and Neurobiology, Xuzhou Medical University , Xuzhou, Jiangsu, China
                [4] 4 Department of Blood Transfusion, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui, China
                [5] 5 Laboratory Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences , Guangzhou, Guangdong, China
                Author notes

                Edited by: Fei Mao, Jiangsu University, China

                Reviewed by: Xudong Tang, Jiangsu University of Science and Technology, China; Hai Long Fu, The First Affiliated Hospital of Soochow University, China

                †These authors have contributed equally to this work

                This article was submitted to Inflammation, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2023.1086898
                9893113
                36742294
                f7390f7e-bb14-4479-b38d-c9152a91d587
                Copyright © 2023 Pan, Lin, Fu, Zeng, Gu, Niu, Fang and Gu

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 01 November 2022
                : 04 January 2023
                Page count
                Figures: 8, Tables: 0, Equations: 0, References: 43, Pages: 11, Words: 4335
                Funding
                This study was supported by the Key Research and Development Program of Xuzhou City (KC22155), the Xuzhou Municipal Health Commission 2020 Youth Medical Science and Technology Innovation Project (XWKYHT20200065), a research foundation for advanced talents of Guandong Provincial People’s Hospital (KJ012021097).
                Categories
                Immunology
                Original Research

                Immunology
                uc,geo dataset,biomarkers,colon cancer,immune
                Immunology
                uc, geo dataset, biomarkers, colon cancer, immune

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