Downregulated annexin A1 expression correlates with poor prognosis, metastasis, and immunosuppressive microenvironment in Ewing's sarcoma

Ewing'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. Highly prognosis-related hub genes were identified by independent progno...

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Bibliographic Details
Published in:Aging (Albany, NY.) NY.), 2023-03, Vol.15 (6), p.2321-2346
Main Authors: Shi, Xiangwen, Wu, Yipeng, Tang, Linmeng, Ni, Haonan, Xu, Yongqing
Format: Article
Language:English
Subjects:
Adolescent
Annexin A1 - genetics
Bone Neoplasms - genetics
Humans
Matrix Metalloproteinase 9
Prognosis
Research Paper
Sarcoma, Ewing - genetics
Tumor Microenvironment - genetics
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Summary:Ewing'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. Highly 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. ANXA1 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
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.204615