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1000 Titel
  • Integrative analysis of key candidate genes and signaling pathways in autoimmune thyroid dysfunction related to anti-CTLA-4 therapy by bioinformatics
1000 Autor/in
  1. Zhang, Ying |
  2. Garofano, Francesca |
  3. Wu, Xiaolong |
  4. Schmid, Matthias |
  5. Krawitz, Peter |
  6. Essler, Markus |
  7. Schmidt-Wolf, Ingo G. H. |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-06-04
1000 Erschienen in
1000 Quellenangabe
  • 38(6):1717-1729
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1007/s10637-020-00952-z |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575511/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), the first immune checkpoint to be targeted clinically, has provided an effective treatment option for various malignancies. However, the clinical advantages associated with CTLA-4 inhibitors can be offset by the potentially severe immune-related adverse events (IRAEs), including autoimmune thyroid dysfunction. To investigate the candidate genes and signaling pathways involving in autoimmune thyroid dysfunction related to anti-CTLA-4 therapy, integrated differentially expressed genes (DEGs) were extracted from the intersection of genes from Gene Expression Omnibus (GEO) datasets and text mining. The functional enrichment was performed by gene ontology (GO) annotation and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Protein-protein interaction (PPI) network, module enrichment, and hub gene identification were constructed and visualized by the online Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. A total of 22 and 17 integrated human DEGs in hypothyroidism and hyperthyroidism group related to anti-CTLA-4 therapy were identified, respectively. Functional enrichment analysis revealed 24 GO terms and 1 KEGG pathways in the hypothyroid group and 21 GO terms and 2 KEGG pathways in the hyperthyroid group. After PPI network construction, the top five hub genes associated with hypothyroidism were extracted, including ALB, MAPK1, SPP1, PPARG, and MIF, whereas those associated with hyperthyroidism were ALB, FCGR2B, CD44, LCN2, and CD74. The identification of the candidate key genes and enriched signaling pathways provides potential biomarkers for autoimmune thyroid dysfunction related to anti-CTLA-4 therapy and might contribute to the future diagnosis and management of IRAEs for cancer patients.
1000 Sacherschließung
lokal Gene Expression Regulation, Neoplastic [MeSH]
lokal CTLA-4
lokal Protein Interaction Maps [MeSH]
lokal Immune checkpoint blockade
lokal Signaling pathway
lokal Humans [MeSH]
lokal Hypothyroidism/genetics [MeSH]
lokal Animals [MeSH]
lokal Autoimmune Diseases/genetics [MeSH]
lokal Gene Ontology [MeSH]
lokal Hypothyroidism/chemically induced [MeSH]
lokal Mice [MeSH]
lokal Preclinical Studies
lokal Immune Checkpoint Inhibitors/adverse effects [MeSH]
lokal Autoimmune Diseases/chemically induced [MeSH]
lokal Differentially expressed genes
lokal Hyperthyroidism/chemically induced [MeSH]
lokal Autoimmune Diseases/metabolism [MeSH]
lokal Signal Transduction [MeSH]
lokal Biomarkers [MeSH]
lokal Computational Biology [MeSH]
lokal CTLA-4 Antigen/antagonists
lokal Hyperthyroidism/genetics [MeSH]
lokal Autoimmune thyroid dysfunction
1000 Liste der Beteiligten
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1000 Erstellt am 2023-11-17T16:05:14.101+0100
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1000 Zuletzt bearbeitet Fri Dec 01 07:49:13 CET 2023
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