ArticleAging2023
Downregulated annexin A1 expression correlates with poor prognosis, metastasis, and immunosuppressive microenvironment in Ewing's sarcoma.
Article in Aging, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 5 citations in OpenAlex.
- Targeting macrophage-associated core genes for prognostic prediction and therapeutic insights in bladder cancer.Discover oncology · 2026Article
- Spatial Profiling Identifies Tumor-Associated Stroma Enrichment and MIF as Potential Immunotherapy Targets in Primary Ewing Sarcomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Decoding the immune landscape in Ewing sarcoma pathogenesis: The role of tumor infiltrating immune cells and immune milieu.Journal of bone oncology · 2025Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveEwing's sarcoma (ES) is a common bone malignancy in children and adolescents that severely affects the prognosis of patients. The aim of this study was to identify novel biomarkers and potential therapeutic targets for ES.
methodsHighly prognosis-related hub genes were identified by independent prognostic analysis in the GSE17679 dataset. We then performed survival analysis, Cox regression analysis and clinical correlation analysis on the key gene and validated them with the GSE63157, GSE45544 and GSE73166 datasets. Differentially expressed genes (DEGs) were screened based on the high and low expression of key gene, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were performed to explore the underlying mechanisms of ES, and significant module genes were established based on protein-protein interaction (PPI) networks. Furthermore, the correlations between module genes and the immune microenvironment were analyzed and the correlations between the key gene and immune infiltration levels in sarcoma were investigated using TIMER and TISIDB. Finally, the expression levels of these key genes in ES cell lines (RD-ES and A673 cells) were further validated by real-time quantitative PCR (RT-qPCR). CCK-8 and EdU assays were performed to assess the effect of ANXA1 knockdown on RD-ES cell proliferation.
resultsANXA1 was identified as a key gene for ES prognosis. The overall survival (OS) time of patients with low ANXA1 expression was shorter, and the expression level of ANXA1 in the metastatic group was significantly lower than that in the primary group (P<0.01). Additionally, the abundance of 12 immune cells in the ANXA1 low-expression group was significantly lower than that in the high-expression group (all P<0.05), which may be related to the inhibition of the immune microenvironment. A PPI network was constructed based on 96 DEGs to further identify the five ANXA1-related module genes (COL1A2, MMP9, VIM, S100A11 and S100A4). The expression levels of ANXA1, COL1A2, MMP9, VIM, S100A11 and S100A4 were significantly different between ES cell lines and mesenchymal stem cells after validation in two ES cell lines (all P<0.01). Among these genes, ANXA1, COL1A2, MMP9, VIM and S100A4 were significantly associated with the prognosis of ES patients (all P<0.05). Importantly, ANXA1 knockdown significantly promoted the proliferation of RD-ES cells, which may explain the susceptibility to ES metastasis in the ANXA1 low-expression group.
conclusionsANXA1 may serve as an independent prognostic biomarker for ES patients and is associated with metastasis and the immunosuppressive microenvironment in ES, which needs to be validated in further studies.
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