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      Dachsous cadherin related 1 (DCHS1) is a novel biomarker for immune infiltration and epithelial-mesenchymal transition in endometrial cancer via pan-cancer analysis

      research-article
      1 , 2 , 3 , 1 , 2 ,
      Journal of Ovarian Research
      BioMed Central
      DCHS1, Immune infiltration, Biomarker, EMT, UCEC

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          Abstract

          Background

          Dachsous cadherin related 1 (DCHS1) is one of calcium-dependent adhesion membrane proteins and is mainly involved in the development of mammalian tissues. There is a lack of more detailed research on the biological function of DCHS1 in pan-cancer.

          Materials and methods

          We evaluated the expression, the prognostic value, the diagnostic value and genomic alterations of DCHS1 by using the databases, including TCGA, UALCAN, HPA, GEPIA2.0 and GSCA. We employed the databases of UCSC, TIMER2.0, TISIDB, GSCA to analyze the association between DCHS1 expression and the immune microenvironment, stemness, TMB, MSI and anticancer drug sensitivity. BioGRID, STRING and GEPIA2.0 were used to perform protein interaction and functional enrichment analysis. Real-time quantitative PCR, CCK8, Transwell assay and Western blot were performed to determine the function of DCHS1 in UCEC.

          Results

          DCHS1 is differentially expressed in many cancers and its expression is significantly associated with tumor prognosis and diagnosis. DCHS1 expression was significantly correlated with the infiltration of cancer-associated fibroblasts (CAFs), Endothelial cell (ECs), and Hematopoietic stem cell in most cancers. In addition, DCHS1 was significantly associated with sensitivity to many antitumor drugs. Functional enrichment analysis revealed that DCHS1-related proteins were involved in Focal adhesion, Endometrial cancer and Wnt signaling pathway. GSEA results showed that DCHS1 was related to epithelial-mesenchymal transition (EMT) in many cancers. In vitro experiments in UCEC showed that DCHS1 regulated cell proliferation, migration and EMT.

          Conclusions

          Our findings indicated that DCHS1 might be a novel prognostic and diagnostic biomarker and immunotherapy target, and plays an important role in the proliferation, migration and EMT in UCEC.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13048-024-01478-1.

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          Most cited references37

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          The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data.

          The cBio Cancer Genomics Portal (http://cbioportal.org) is an open-access resource for interactive exploration of multidimensional cancer genomics data sets, currently providing access to data from more than 5,000 tumor samples from 20 cancer studies. The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications. © 2012 AACR.
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            TIMER2.0 for analysis of tumor-infiltrating immune cells

            Abstract Tumor progression and the efficacy of immunotherapy are strongly influenced by the composition and abundance of immune cells in the tumor microenvironment. Due to the limitations of direct measurement methods, computational algorithms are often used to infer immune cell composition from bulk tumor transcriptome profiles. These estimated tumor immune infiltrate populations have been associated with genomic and transcriptomic changes in the tumors, providing insight into tumor–immune interactions. However, such investigations on large-scale public data remain challenging. To lower the barriers for the analysis of complex tumor–immune interactions, we significantly improved our previous web platform TIMER. Instead of just using one algorithm, TIMER2.0 (http://timer.cistrome.org/) provides more robust estimation of immune infiltration levels for The Cancer Genome Atlas (TCGA) or user-provided tumor profiles using six state-of-the-art algorithms. TIMER2.0 provides four modules for investigating the associations between immune infiltrates and genetic or clinical features, and four modules for exploring cancer-related associations in the TCGA cohorts. Each module can generate a functional heatmap table, enabling the user to easily identify significant associations in multiple cancer types simultaneously. Overall, the TIMER2.0 web server provides comprehensive analysis and visualization functions of tumor infiltrating immune cells.
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              TISIDB: an integrated repository portal for tumor–immune system interactions

              The interaction between tumor and immune system plays a crucial role in both cancer development and treatment response. To facilitate comprehensive investigation of tumor–immune interactions, we have designed a user-friendly web portal TISIDB, which integrated multiple types of data resources in oncoimmunology. First, we manually curated 4176 records from 2530 publications, which reported 988 genes related to anti-tumor immunity. Second, genes associated with the resistance or sensitivity of tumor cells to T cell-mediated killing and immunotherapy were identified by analyzing high-throughput screening and genomic profiling data. Third, associations between any gene and immune features, such as lymphocytes, immunomodulators and chemokines, were pre-calculated for 30 TCGA cancer types. In TISIDB, biologists can cross-check a gene of interest about its role in tumor–immune interactions through literature mining and high-throughput data analysis, and generate testable hypotheses and high quality figures for publication. http://cis.hku.hk/TISIDB Supplementary data are available at Bioinformatics online.
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                Author and article information

                Contributors
                sd.wangqian@163.com
                Journal
                J Ovarian Res
                J Ovarian Res
                Journal of Ovarian Research
                BioMed Central (London )
                1757-2215
                9 August 2024
                9 August 2024
                2024
                : 17
                : 162
                Affiliations
                [1 ]Department of Clinical Laboratory, Qilu Hospital of Shandong University, ( https://ror.org/056ef9489) Jinan, Shandong China
                [2 ]Department of Clinical Laboratory, Qilu Hospital of Shandong University (Qingdao), ( https://ror.org/056ef9489) No.758 Hefei Road, Qingdao, 266035 Shandong China
                [3 ]GRID grid.410645.2, ISNI 0000 0001 0455 0905, Department of Gynecology, Qingdao Women’s and Children’s Hospital, , Qingdao University, ; Qingdao, Shandong China
                Article
                1478
                10.1186/s13048-024-01478-1
                11312386
                39123216
                29fc2441-181a-4cc5-ace7-6eabdf5435e4
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 11 August 2023
                : 15 July 2024
                Funding
                Funded by: Qingdao Outstanding Health Professional Development Fund
                Funded by: Flexible Talent Fund of Qilu hospital of Shandong University
                Award ID: QDKY2021RX03
                Funded by: Qingdao Science and Technology Demonstration and Guidance Project
                Award ID: 22-3-7-smjk-10-nsh
                Funded by: FundRef http://dx.doi.org/10.13039/100019558, Qingdao Key Health Discipline Development Fund;
                Categories
                Research
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Obstetrics & Gynecology
                dchs1,immune infiltration,biomarker,emt,ucec
                Obstetrics & Gynecology
                dchs1, immune infiltration, biomarker, emt, ucec

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